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The Role of Gastric Acid in Preventing Foodborne Disease and How

The Role of Gastric Acid in Preventing Foodborne Disease and How

1292

Journalof Food Protection, Vol. 66, No. 7, 2003, Pages 1292– 1303

Review TheRole ofGastric inPreventing Foodborne Disease and HowBacteria Overcome Acid Conditions †

JAMES L.SMITH

U.S.Department of Agriculture,Agricultural Research Service, EasternRegional Research Center,600 East Mermaid Lane, Wyndmoor, Pennsylvania19038, USA Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 MS02-392:Received 24October 2002/ Accepted 7February2003

ABSTRACT

Thesecretion of by the plays an important role in protecting the body against pathogens ingestedwith food or water .Agastric uidpH of 1to2 isdeleterious to many microbial pathogens; however ,theneutralization ofgastric acid by or the inhibition of acid by various drugs may increase the risk of food- or waterborne illnesses. is often treated by decreasing or eliminating gastric acid secretion, and such treatment blocks theprotective antibacterial action of gastric uid.The majority of pepticulcer disease cases originate from Helicobacterpylori infections.T reatmentof H. pylori–inducedpeptic ulcers with antibiotics reduces the need for drugs that inhibit gastric acid secretionand thereby diminishes the risk of food- and waterborne illness for peptic ulcer disease patients. Many bacterial pathogens,such as Escherichiacoli, Salmonella Typhimurium,and H. pylori, cancircumvent the acid conditions of thestomach bydevelopingadaptive mechanisms that allow these bacteria to survivein acidenvironments. As a consequence,these bacteria cansurvive acidic stomach conditions and pass into the intestinal tract, where they can induce gastroenteritis.

Thestomach has a fundamentalrole in killing or in- thegastric mucosal surfaces. The parietal cells deliver H 1 activatingpathogens present in food or water before they and Cl2 intocanaliculi, which crisscross the cellular cyto- enterthe intestinal tract. The stomach is a large-capacity plasm.The canaliculi make up an interconnecting system organlocated between the and the oflabyrinthinechannels lined by microvilli. The canaliculi andfunctions as a reservoirfor thestorage, mixing, minc- openonto the luminal surface to deliver the ing,and partial of food before it moves into the acidsecretions into the gastric gland lumen, and acid is intestinaltract. In addition, the stomach is theprimary site eventuallydelivered to the stomach lumen (42,49, 61). for hydrochloricacid (HCl) secretion (1). GastricHCl en- Theneurotransmitter , the gas- hancesthe absorption of dietary calcium and iron and ac- trin,and the paracrine (hormone-like) are endog- tivatespepsinogen to , which is involved in the par- enouschemicals that act in concert to stimulateand control tialhydrolysis of (1). Mostimportantly, gastric acidproduction by bindingto parietalcell surface receptors HClis a majordefense mechanism against pathogens that (1,42, 49, 104). Acidsecretion is also dependent on oxy- maybe ingested with food or water (48, 49). Gastricjuice gen,calcium, and cyclic AMP (cAMP) (87–89). The bind- has a pH of #1withHCl levels of 150 to 160 mEq/ liter ingof acetylcholine, histamine, and to the parietal (5,475to 5,840 mg/ liter),and the stomach produces 1 to2 cellreceptors results in an increasein intracellularcalcium. litersof gastric juice per day (1, 49). Inthis review, the Histamineactivates adenylate cyclase, which catalyzes the roleof gastric acid as an antibacterial agent and the con- synthesisof cAMP from ATP (42,49, 89). Calcium and sequencesof preventing the secretion of or neutralizing the cAMP-dependentprotein kinases are involved in the acti- acidin the stomach with regard to antibacterialactivity and vationof the acid-secreting (42,84, 87, 112). themechanisms by which bacteria increase their resistance Thebasic mechanisms involved in acid secretion by toacid environments, including that of the stomach, are theparietal cell are presented in Figure 1. discussed. diffusesinto the parietal cell from theblood side of thecell 2 1 HCL SECRETION BYTHESTOMACH andcombines with water toform HCO 3 and H through thereaction catalyzed by . The bicar- HClis secreted from theparietal cells located in the bonatepasses out of the parietal cells into the in gastricglands. These glands open into the on 2 2 exchangefor chlorideions via the HCO 3 /Cl exchange .Chloride ions are eventually released from thepa- *Authorfor correspondence. Tel: 215-233-6520; Fax: 215-233-6581; rietalcells into the lumen of thegastric gland via a chloride E-mail: [email protected]. †Mentionof abrandor Žrm name doesnot constitute an endorsement by ionchannel. ions are released into the gastric 1 theU.S. Department ofAgriculture over others of a similar naturenot glandlumen in exchange for K ionsthrough the action of mentioned. the H1/K1-ATPase(i.e., the proton pump). One hydrogen J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1293

scopicallyexerted a killingeffect on Salmonella Typhi and thatthe addition of artiŽ cial containing nitrite to the gastric uidenhanced the killing of the organism. The ex- perimentsreported by Benjamin et al. (11), Dykhuizenet al. (31), McKnightet al. (64), and Xu et al. (120) strongly suggestthat salivary nitrite and the gastric acid of thestom- achact synergistically to inactivate foodborne pathogens priorto the entry of these pathogens into the gastrointes- tinaltract. Archer (2) hasrecently reviewed the role of sal- ivarynitrite potentiation of theantibacterial action of stom- ach acid.

NEUTRALIZING GASTRIC ACID ORINHIBITING Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 GASTRIC ACID SECRETION Thereare a numberof ways to reduce gastric acid or inhibitits formation. HCl secreted by the stomach can be neutralizedthrough the oral administration of absorbable FIGURE 1. Mechanismsinvolved in the secretion of HCl bypa- rietalcells. antacidssuch as sodium or calcium carbonate. Nonabsorbableantacids such as aluminum hydroxide or magnesiumhydroxide are also effective in neutralizing ionis exchanged for apotassiumion for eachA TPmole- stomachacid (66). Acidsecretion by the stomach can also culehydrolyzed. The cytosolic K 1 istransported back into becontrolled surgically. V agotomyis the surgical cutting thegastric gland lumen via K 1 ionchannels (42, 49) (Fig. ofcertain branches of the vagus nerve, thereby preventing 1). therelease of acetylcholine,which is apotentstimulator of gastricacid secretion. Another surgical procedure, gastrec- ROLEOF SALIVARY NITRITEIN GASTRIC ACID tomy,the removal of all or part of the stomach, results in ANTIBACTERIAL ACTION alossof the acid-secreting parietal cells (1, 49). Anumberof studies have indicated that acidic gastric Cholinergic(muscarinic) receptor antagonists block juiceis moreeffective in killingbacteria if nitriteis present. gastricsecretion by bindingto theM 1 muscarinicreceptors Themajor sources of nitrite in the human diet are fruits, onpostganglionic neurons to prevent the release of acetyl- vegetables,cereals, and water containing nitrate (29, 64). cholineand its subsequent binding to parietal cells (99). Ingestednitrate is absorbed from thegastrointestinal tract Anticholinergicagents that inhibit acid secretion include intothe circulatory system, and up to 25% of this nitrate atropine,, glycopyrrolate, and propantheline. iseventually concentrated in the salivary glands. Nitrate is Histamine H2 receptorantagonists are competitive and re- thensecreted in the saliva, in which it is reducedto nitrite versibleinhibitors of gastric acid secretion. These com- bymouthbacteria (28,29, 64). Nitriteis mixed with gastric poundsinhibit the binding of histamineat thehistamine H 2 juicewhen saliva is swallowed.The major sources of nitrite receptorsites on the parietal cells (98, 99). ,ra- inthe human diet are not foods containing nitrite that was nitidine,, and nizatidine are histamine H 2 antag- addedduring processing, but foods that naturally contain oniststhat effectively inhibit gastric acid secretion. The nitrate. substitutedbenzimidazoles, , and Withthe use of conditions simulating a normalstom- (protonpump inhibitors) prevent gastric acid secretion by ach,Dykhuizen et al. (31) demonstratedthat Salmonella inhibitingthe enzyme H 1K1-ATPase(i.e., the proton Enteritidis, Salmonella Typhimurium,and Yersiniaentero- pump).These compounds are acid-active prodrugs that colitica were killedafter 30 min of exposure to nutrient noncompetitivelyb indand i rreversiblyi nactivateth e brothacidiŽ ed to pH 2.1 with HCl. Under the same con- ATPaseby binding covalently to two cysteine residues of ditions, Shigellasonnei and Escherichiacoli O157survived the enzyme (88, 98). unlessnitrite was present.The level of bacteria used was Nalin et al. (70), ina studyinvolving volunteers who ca. 107 CFU/ml.In nutrient broth acidiŽ ed to pH 3.0, the ingested Vibriocholerae, foundthat heavy smokers of can- additionof nitrite was necessaryto kill all of the bacteria nabishad decreased levels of stomach acid and were more testedby Dykhuizenet al. (31). Otherworkers showed that susceptibleto the induced by V. cholerae than nitritepresent in nutrient broth acidiŽ ed to a pHof 3.0 to were lightsmokers or nonsmokers.Gastrin- and histamine- 3.3was microbicidalto E. coli and Candidaalbicans ; how- inducedgastric acid synthesis is inhibited by the binding ever,acidconditions in the absence of nitrite did not lead ofcannabinoidsto CB 1 receptors (78). Feverhas also been tothe killing of these pathogens (11, 120). Theseauthors reportedto inhibit gastric acid secretion (48). Cytokines concludedthat salivary nitrite present in gastric  uidmay stimulatethe synthesis of prostaglandins,particularly pros- playan important role in a host’s defenseagainst ingested taglandin E2,whichis considered the ultimate endogenous pathogens. inducerof the febrile response (97). Prostaglandinsprevent Datafrom anunpublished thesis cited by McKnight et gastricHCl secretion by inhibiting adenylate cyclase syn- al. (64) indicatethat human gastric  uidobtained endo- thesisof cAMP (42, 112). 1294 SMITH J.FoodProt., Vol. 66, No. 7

DISEASE STATESTHAT INDUCE food).Emptying times for olderindividuals were acceler- HYPOCHLORHYDRIA ORACHLORHYDRIA atedcompared with those for youngerpersons (50.4 min versus96.0 min, respectively, for liquid;104.4 min versus Anumberof factors can lead to hypochlorhydria (i.e., 124.8min, respectively, for solidfood) (41). Incontrast, alowlevel of HCl in the stomach) or (i.e., a whenClarkston et al. (18) comparedgastric emptying times lackof HCl in the stomach) with a concurrentdecrease or for individualsaged 23 to 50 years (mean age, 30 years) lossof thegastric acid protective mechanism. For example, withthose for individualsaged 70 to 84yearsof age(mean autoimmuneand environmental atrophic gastritis can result age,76 years), they found that the elderly group had sig- ina lossof acid secretion. Autoimmune atrophic gastritis niŽcantly longer emptying times for bothliquids (47 min isa geneticdisease in which there is an immune response versus35 min) and solids (182 min versus 127 min) than againstthe parietal cells (121). Theloss of theparietal cells didthe younger group. In total, 65 individualswere studied leadsto achlorhydria as well as to the loss of the parietal byGraff etal. (41) andClarkston et al. (18), and the con- cell–derived that facilitates vitamin B 12 ab- ictingresults obtained with respect to the effect of aging Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 sorption.Therefore, individuals with autoimmune atrophic ongastric emptying may be due to the small number of gastritiswill develop pernicious anemia (121). There is no individualsstudied and to physiological differences be- treatmentfor theachlorhydria of autoimmuneatrophic gas- tweenthe two populations. tritis,but pernicious anemia can be treatedwith regular vi- Theentrance of food into the stomach leads to a tran- tamin B12 injections. sientelevation in gastricpH. The median fasting gastric pH Environmentalatrophic gastritis is a form ofchronic for agroupof elderly individuals ( n 5 79;mean age, 71 gastritisassociated with environmental factors, such as a years;range, 65 to 83 years) was 1.3,compared with 1.7 dietcontaining a highlevel of pickled vegetables, salted for agroupof young individuals ( n 5 24;mean age, 25 Žsh,or smoked meat or Helicobacterpylori infection (121). years;range, 21 to 35 years). After astandardmeal com- Gastricacid secretion may be reduced in environmental prisinghamburger ,bread,potatoes, and milk, the peak gas- atrophicgastritis, but it does not disappear completely; an- tricpH for theelderly group reached 6.2, compared with tiparietalcell antibodies are not present (121). More than 6.6for theyoung group (26, 86). Thetimes taken for the 50%of patientswith an acute H. pylori infectionwill have gastricpH to return to 2.0 were 100min for theyoung atransienthypochlorhydria for approximately4 months groupand 150 min for theelderly group. Thus, the fasting (range,2 to8 months) (45, 118). Interleukin1 b (IL-1b) is gastricpH and the peak pH reached after the ingestion of upregulatedby H. pylori infection;interleukin 1 b is a po- amealwere onlyslightly higher for theyoung group than tentinhibitor of gastricacid secretion and may explain why for theelderly group; however ,thetime taken for thegastric hypochlorhydriais induced by H. pylori infection (33). An- pHto return to 2 was signiŽcantly longer for theelderly tibiotictreatment will eliminate H. pylori, witha resultant population.Both study groups contained men and women, correctionof the hypochlorhydric state. Individuals expe- andDressman etal. (26) andRussell et al. (86) found no riencinghypochlorhydria or achlorhydria are more suscep- signiŽcant differences with respect to gender in their re- tibleto infectionsfrom foodor waterborneagents (see ‘‘Ef- sults. fectof Gastric Acidity on Enteric Pathogens’ ’ section). Theeffect of an increase or decrease in gastric emp- EFFECTOF FOODONGASTRIC EMPTYING AND tyingtime or of the temporary elevation of the gastric pH GASTRIC ACIDITY onthesurvival of bacteriain thestomach has received little attention.It is logical to assumethat if the gastric emptying Gastricemptying time, that is, the length of timefood timeis short, as it is for liquids,then pathogens have less remainsin the stomach, is in uenced by certain character- contactwith gastric acid and viable organisms may pass isticsof food. Ingested liquids begin to empty into the du- throughthe stomach into the intestine. While there are no odenumalmost immediately, whereas solid foods leave the dataavailable concerning the effect of a temporaryincrease stomachonly after a lagperiod during which they are re- instomach pH after eating on the survival of bacteria,it is ducedto 1- to 2-mm particles (1, 49). Theemptying rate possiblethat if a returnto more acid conditions is slow, for bothsolids and liquids depends on the chemical com- organismsmay be better able to survive and pass into the positionof these materials. A highlevel of fat, a lowpH, intestinaltract. ahighviscosity, and/ orahighcaloric content delay gastric EFFECTOF FOOD ONPATHOGEN SURVIVAL emptyingof the ingested materials (49, 63). Studiessuggest that both gender and age in uence gas- Ina studyinvolving the inoculation of the acid-sensi- tricemptying. However ,theeffect of age on gastric emp- tiveenteric pathogens Salmonella Typhimurium , Salmonel- tyingis not clear ,sincecon icting results have been ob- la Typhi,Campylobacterjejuni, and V. cholerae (at ca. 106/ tained.Graff etal. (41) studiedthe time required for water 0.1g) individually onto ground beef, W atermanand Small oran omelet meal to clear the stomach by comparing the (117) foundthat the organisms survived for atleast 2 hat processfor youngmen and women (i.e., 20 to30yearsold) 378CinLuria-Bertani broth acidiŽ ed to pH 2.5 with HCl; withthat for oldermen and women (i.e., 38 to 53 years inthe absence of ground beef, the organisms did not sur- old).Gastric emptying was signiŽcantly slower for women vivethe 2-h acid treatment. When the acid-sensitive enteric thanfor men(77.4 min versus 75.6 min, respectively, for pathogenswere inoculatedonto boiled rice or boiled egg liquid;112.8 min versus 104.4 min, respectively, for solid white,only the pathogens inoculated onto boiled egg white J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1295 survivedin pH 2.5 broth. W atermanand Small (117) pos- (23, 45). Aquadrupletreatment incorporating a proton tulatedthat a highprotein content in a foodmay protect pumpinhibitor (i.e., an inhibitor of the enzyme H 1K1- bacteriaagainst the killing effects of gastric acid. ATPase) alongwith bismuth and two antibiotics (see above) Fischerrats were usedby Drouaultet al. (27) to model canbe used if the triple therapy does not eradicate the or- theeffect of food on the gastric acid killing of bacteria. ganism (55). Therefore,only ulcers that are not caused by When 109 CFU of Lactococcuslactis perml was fedto H. pylori infectionsor arerefractory to antibiotictreatment ratsin the absence of food, only 7% of the organisms sur- shouldbe treated with drugs that neutralize or prevent the vivedin the stomach. However ,when L. lactis was mixed secretionof gastric acid. withthe rats’ food, 100% of the organisms survived. Drouaultet al. (27) postulatedthat the acid-buffering ca- EFFECTOF GASTRIC ACIDITY ON pacityof the rat diet protected the lactococci against the ENTERIC PATHOGENS killingeffect of gastric acid. Mostingested enteric pathogens are quite susceptible Gastric uidobtained from fastinghealthy volunteers toacidic gastric juice, but this susceptibility decreases if Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 3 andadjusted to pH 1.5 with HCl killed approximately 10 thehost has undergone a gastrectomyor is taking drugs enterotoxigenic E.coli,Shigella  exneri, and Salmonella thatneutralize gastric acid or inhibit gastric acid secretion. Typhimuriumcells within 5 minat room temperature (79). However,therewas anapproximately two- to fourfold in- Bacteria. Individualswith hypochlorhydria or achlor- creasein survival after 5 minwhen the enteric pathogens hydriaresulting from malnutritionor a priorgastrectomy were suspendedin postfeeding gastric  uidadjusted to pH were foundto be moresusceptible to infectionwith V. chol- 1.5.The gastric  uidwas collectedfrom thevolunteers 20 erae andoften had a moresevere disease (38,90, 92). Vol- minafter they had ingested a mealof steak and toast (79). unteerswho drank an inoculum of V. cholerae (108 CFU) Thus,Peterson et al. (79) demonstratedthat postmeal gas- withbicarbonate demonstrated a higherattack rate than vol- tric uidwas lesseffective in killing bacteria. Since the unteerswho consumed the organisms without bicarbonate. postmealgastric  uidwas adjustedto pH 1.5,the protective Inaddition, bicarbonate decreased the number of bacteria effectwas notsimply due to buffering of the gastric  uid necessaryto cause disease from 10 8 to 104 organismsper acidby the food. Peterson et al. (79) didnot speculate on individual (15, 46). Themean decimal reduction times for howfood protected the bacteria from gastricacid. threestrains of V.vulniŽcus exposedto simulated gastric Whilethe mechanism is not completely clear ,itis ap- juiceat pH 4.0 and at pH 3.0 were 3.3and 1.3 min, re- parentthat certain foods do protect bacteria from acidic spectively.However , V.vulniŽcus strainsdid not survive if conditionsand from gastricacidity in vitro.More research, thepH ofthesimulated gastric juice was loweredto 2 (54). particularlyresearch involving in vivoexperiments, is need- For patientswith acute salmonellosis, morbidity and edto assess how foods protect bacteria from theacid en- mortalityrates were highestfor thoseindividuals who had vironmentof the stomach. previouslyundergone a gastrectomy (44,72, 74, 116). Re- centtreatment with histamine H 2 antagonistswas associated PEPTICULCER DISEASE witha twofoldincrease in the risk of Salmonella infections Theantibacterial action of gastricacid may fail during (72). Withthe use of aspirated gastric juice obtained from certaincourses of treatment for pepticulcer diseases such achlorhydricpernicious anemia patients or from normalin- asgastric and duodenal ulcers. A pepticulcer is character- dividualsand adjusted to a pHof either 2.0 or 4.0, Gian- izedby an area of acid and pepsin damage to the mucous nella et al. (37) foundthat ca. 10 9 Salmonella Typhimu- membranethat penetrates through the muscularis mucosa rium, Salmonella Paratyphi,or Salmonella Enteritidiscells ofthestomach or otherparts of thedigestive system. In the perml were killedin about 30 min at pH 2.0 but survived UnitedStates, the lifetime prevalence of peptic ulcer dis- for atleast 120 min at pH 4.0. The killing of Salmonella easeis about 10% (1);approximately500,000 new cases speciesin pH 6.8 gastric juice collected from pernicious and4,000,000 recurrences of gastric and duodenal ulcers anemiapatients and adjusted to pH 2.0with HCl indicated occureach year (113). Sincepeptic ulcer disease occurs thatthe major killing action of gastric juice resides in the onlyif thestomach secretes acid, it is generallytreated with HCl content (37). As anotherexample, a 5.5-log 10 decrease antacids, H2 receptorantagonists, proton pump inhibitors, inthe number of Salmonella TyphimuriumDT104 cells orother inhibitors of gastric acid secretion (113); such was observedwithin 5 minin simulated gastric  uidad- treatmentsincrease the risk of food- or waterborne illness justedto pH 1.5 (83). (see ‘‘Effectof GastricAcidity on EntericPathogens’ ’ sec- Theuse of omeprazole, a protonpump inhibitor ,pre- tion). disposesindividuals to Campylobacter infections (73). The H. pylori hasbeen identiŽ ed as the etiologic agent for useof this drug was associatedwith a 10-foldincrease in .90%of duodenalulcers and ca. 80% of gastric ulcers (39, therisk of infection. No risk of campylobacteriosis was 45).H. pylori infectioncan be effectively eliminated by notedwith the use of histamine H 2 antagonists.Proton treatmentwith antibiotics, which is usually followed by pumpinhibitors reduce gastric acidity to a greaterextent rapidhealing of the ulcers. The use of a tripleregimen thanhistamine H 2 antagonistsdo (89). consistingof a bismuthsalt combined with metronidazole Ina foodborneoutbreak of hospital-acquiredlisteriosis (or clarithromycin)and tetracycline (or amoxicillin)is gen- inBostonhospitals, patients receiving antacids or histamine erallysuccessful in eradicating H. pylori from thestomach H2 antagonistswere morelikely than control patients to be 1296 SMITH J.FoodProt., Vol. 66, No. 7 infectedwith Listeriamonocytogenes (43). Cobb et al. (19) cosaduring hypochlorhydria. Results obtained by Doglioni notedthat there was anincreased prevalence of L. mono- et al. (25) for gastricbiopsy specimens isolated from Italian cytogenes fecalcarriage for femalepatients receiving long- patientsundergoing upper gastrointestinal endoscopy indi- termtreatment with histamine H 2 antagonists.The treated catedthat 0.27% (41 of 15,023)of thepatients involved in patientshad a carriagerate of 20%, compared with a rate thestudy had gastric giardiasis. All 41 patients were suf- of2.1% for controlpatients; however ,listeriosisdid not feringfrom chronicatrophic gastritis, and 37 of these pa- developin any of the patients (19). Animalexperiments tientswere infectedwith H. pylori. Hypochlorhydriais a conductedby Schlechet al. (93) indicatedthat the reduction featureof atrophic gastritis due to adecreasein the number ofgastricacidity by thehistamine H 2 antagonistcimetidine ofparietal cells, and H. pylori infectionscan induce hy- loweredthe dose of L.monocytogenes necessaryto induce pochlorhydria.In addition, 5 of41 patients were being aninvasive infection in rats. The oral 50% infective dose treatedwith antacids (25). Thedecreased gastric acidity al- for animalstreated with cimetidine was 10 2 CFU, compared lowedthe colonization of thestomach by G. lamblia. Sanad withan oral 50% infective dose of 10 6 CFU of L. mono- et al. (91) alsoreported that under conditions of reduced Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 cytogenes for untreatedrats (93). Roeringet al. (83) dem- gastricacidity, gastric giardiasis may occur in conjunction onstratedthat three strains of L.monocytogenes at 6 log10 withintestinal giardiasis. CFU/mlwere killedby 30 min of exposure to simulated Itis probable that the environmentally resistant forms gastricjuice at pH1.5.These data suggest that gastric acid (i.e.,oocysts, cysts, and eggs) of foodborne parasites such isbactericidal to L.monocytogenes andthat drugs that in- as Cryptosporidium,Cyclospora, Giardia, Taenia, and hibitor neutralizegastric acid increase the susceptibility of Toxoplasma survivepassage through the stomach. Most individualsto infection by this organism. Toxoplasma infectionsare acquired through the ingestion Ina nursinghome outbreak caused by E. coli O157: ofmeat from infectedanimals in which the parasite had H7,elderly patients who had previously undergone a gas- encystedin the tissues as walled bradyzoites. Asymptom- trectomyhad an increasedrisk of infection (14). An E. coli atic Toxoplasma infections(evidenced by seropositivity) O157:H7outbreak in central Scotland revealed that one of arecommon in meat-eating populations including that of therisk factors for hemolyticuremic syndrome was hypo- theUnited States (101), andMead et al. (65) stated that chlorhydriadue to agastrectomyor the use of proton pump approximately40% of individualsin theUnited States $60 inhibitorsand/ orhistamine H 2 antagonists (30). Hypochlor- yearsof age are seropositive for Toxoplasma. Thus, the hydriawas signiŽcantly associated with death for thesehe- highprevalence of Toxoplasma seropositivityin humans molyticuremic syndrome patients. Arnold and Kaspar (3) indicatesthat bradyzoites of Toxoplasma areresistant to demonstratedthat four of Ž vestrains of E. coli O157:H7 gastricacid even though they lack the extreme resistance survivedfor 3hinsynthetic gastric juice at pH 1.5. In of Toxoplasma oocysts (101). simulatedgastric juice at pH 1.5, three strains of E. coli Viruses. Thehalf-life infectivity of several rotavirus O157:H7survived for atleast 2 h,in contrast to survival strainssuspended in pH 1.8 human gastric  uidwas #1 timesof 5 minfor strainsof Salmonella TyphimuriumDT min (119). Nonetheless,human rotaviruses have been de- 104and 30 min for strainsof L.monocytogenes(83). With tectedin the stools of 35 to 52% of infants and young theuse of an in vitro system to model the gastric acid childrenhospitalized with acute gastroenteritis but less of- inactivationof an E. coli O157:H7strain, T akumiet al. tenin older children and adults with gastroenteritis (50). (108) estimatedthat 20 to 80% of the ingested organisms Morethan 90% of children have rotavirus antibodies by wouldreach the small intestine in a viablestate. Thus, the age 3 (7). Gastricacid production in response to food and (3), invitro data obtained by Arnold and Kaspar Roering hormonalstimulation is normal in healthy infants (100). (83), (108) E. coli et al. andT akumiet al indicatethat However,thebuffering action of milkand the short gastric O157:H7can survive the low pH of the stomach and pass emptyingtime for infants (81) maypermit the rapid passage intothe intestine. ofa rotavirusthrough the infant stomach. Thein uence of surgery or drugs that induce hypo- HepatitisA viruswas foundto retain infectivity in tis- chlorhydriaor achlorhydria on enteric infections has been sueculture after exposure for 5htopH 1.0KCl-HCl buffer wellstudied; however ,thein uence of malnutritionon gas- atroom temperature and for upto 90 min after exposure tricacid secretion has received little attention. Nalin et al. at 388C (94). Thedata obtained by Scholz et al. (94) sug- (71) and Cook (20) suggestedthat malnutrition-induc edhy- gestthat hepatitis A virusmay survive passage through the pochlorhydriais common in developing countries and ac- acidstomach. However ,moreresearch is needed to deter- countsfor theprevalence of enteric diseases in thosecoun- minewhether food- and waterborne viruses are effectively tries.Elderly individuals have a numberof risk factors, e.g., inactivatedby gastric acid in vivo. typeof medication,changes in mental status, and digestive disorders,that lead them to reduce their nutrient intake suf- INDUCTION OFACID RESISTANCE IN Žcientlyto cause malnutrition (102) withpossible hypo- FOODBORNE PATHOGENS chlorhydria,which may make them more susceptible to en- tericillness. Whilehypochlorhydria and achlorhydria are conducive tofoodborne illness, not all cases of illness are due to de- Parasites. Trophozoitesof Giardialamblia, which are creasedgastric acidity in the affected individuals. Healthy notresistant to gastric acid, can colonize the stomach mu- peoplewith no gastric problems may develop foodborne J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1297 diseasesbecause many pathogens have mechanisms that al- isrequired for thelow-pH induction of asubsetof protec- lowthese pathogens to adapt to acidic conditions (34). For tiveASPs andis an ASPitself; phoP mutantsare acid sen- example,the neutrophilic Salmonella Typhimuriumand E. sitive (8). coli havea preferencefor livingand growing at a neutral Salmonella Typhimurium:stationary-phase ATR in pHbut also have a varietyof adaptive mechanisms that minimalmedium. TheASPs andregulatory proteins in- allowthem to respond to potentiallylethal challenges posed volvedin stationary-phase A TRaredifferent from those byacid stresses present in the external environment or in involvedin log-phase A TR.As thecells enter the stationary theanimal host. Studies on acid resistance indicate that phase,a generalstress response that is pH independentbut growthphase, growth conditions, and prior exposure to an ss dependentis induced.Non– acid-adapted Salmonella Ty- acidicpH all play important roles in the development of phimuriumin the stationary phase are at least 1,000-fold acidresistance in bacteria. moreacid resistant than log-phase cells and can tolerate pH s

Salmonella Typhimurium:log-phase ATR inmini- 3.0for approximately4 h (4). Inaddition to the s -regu- Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 mal medium. Thelog-phase acid tolerance response (A TR) latedgeneral stress response, there is also an acid-induced isinduced by the growth of Salmonella Typhimuriumat ATRinstationary-phase cells. Stationary-phase cells that pH4.5to 5.8, which allows the cells to survivesubsequent areacid shocked at pH 4.5can tolerate longer exposures to exposureto a pH3.0 environment for severalhours. Prior pH3.0 than non– acid-shocked cells can. This acid-induc- growth of Salmonella Typhimuriumin a mediumacidiŽ ed iblestationary-phase A TRis ss independentbut does de- withan inorganic acid such as HCl allows the cells to sur- pendon the two-component response regulator OmpR. vivenot only exposure to HCl but also exposure to volatile Acidshock induces the production of OmpR, which in its fattyacids such as acetic acid. Prior growthof theorganism phosphorylatedstate activates the expression of genesnec- inthe presence of volatilefatty also provides protec- essaryfor acid-inducedstationary-phase A TR (5, 6). Sta- tionagainst HCl (4). Inaddition, the exposure of log-phase tionary-phase Salmonella Typhimuriumcells with inser- cellsto an acid stress protects them against a numberof tionalmutants in the ompR geneare acid sensitive, and the otherstresses, such as oxidative stress or heatstress. How- acid-induciblestationary-phase A TRisalmost completely ever,exposureto oxidative stress or otherstresses does not eliminated (4). Theacid-inducible A TRiscomplex, with leadto protection against acid stress (4, 57). ca.50 ASPs (OmpR isalso an ASP) beinginduced during Thelog-phase A TRinvolvesthe induction of emer- stationary-phaseacid shock. There is littleoverlap between gencypH homeostasissystems by mildacid treatment (with ASPs involvedin acid-induced log-phase A TRandthose a pH of .4.5),which allows the cells to maintain an in- involvedin acid-induced stationary-phase A TR (4–6). ternal pH of .5.0as theorganisms encounter a moresevere E. coli and S.  exneri. Similarto the case for Sal- externalpH. Several inducible decarboxylases monella Typhimurium,log-phase A TR,stationary-phase contributeto emergency internal pH maintenance in Sal- ATR,andthe stationary-phase general stress responses are monella Typhimurium.Emergency pH homeostasis,in turn, present in E.coli.S. exneri doesnot have a detectiblelog- allowsthe synthesis of acid shock proteins (ASPs) atpHs phaseor stationary-phase A TRbutdoes demonstrate the of #4.5.Approximately 60 ASPs areformed, and these generalstationary-phase stress response (34,59, 62). Sim- ASPs protectthe cellular machinery against acid damage ilarto the case for Salmonella Typhimurium,log-phase E. (4, 9, 62). Threeregulatory proteins control the expression coli O157:H7exposed to an acidic pH (pH 5.0for 4h) ofdistinct sets of ASPs inlog-phase A TR:thealternative were protectedagainst other stresses. The thermal and NaCl sigmaS factor( ss)(encodedby rpoS),thetwo-component tolerancesof acid-adapted cells were moreextensive than sensorregulatory system PhoP/ Q(encodedby phoP and thoseof non– acid-adapted cells (17). phoQ),andthe ferric uptakeregulator Fur (encodedby fur) (35). Arapidshift to acid shock conditions for Salmonella E. coli and S.  exneri:log-phaseacid habituation. Typhimuriumincreases the transcription of ss, and at the E. coli grownto the log phase in nutrient broth at pH 5.0 sametime the concentration of ss increasesdue to de- survivedexposure to pHsof 3.0to 3.5, whereas cells grown creasedproteolytic turnover .Increasedlevels of ss drive atpH 7.0did not. Cells grown at pH 5.0 survived exposure (9, 34, 40). theexpression of ss-dependentASPs, therebyleading to an topH 3.5 for 25min or to pH 3.0 for 7min increasein acid stress tolerance (4, 10). Acidhabituation can also be induced in cells grown at pH 7.0in nutrient broth if glucose, glutamate, aspartate, FeCl , Fur normallyacts as a repressorof gene expression 3 KCl, or L-prolineis added to log-phase cells (34,40, 85). whenit is bound to intracellular iron, but under acid shock conditions,Fur controlsthe synthesis of a subsetof ASPs E. coli and S.  exneri:acidresistance. Acid resis- inan iron-independent manner .Itis not known how Fur tance(AR) systems,found in stationary-phase cells grown mediatesASP synthesis (4, 34). Theregulators ss, Fur, and incomplex media, permit the survival of E. coli and S. Ada (the ada geneis involved in DNA repairbut not in  exneri whenthey are exposed to pH 2. There are three ASP synthesis; ada mutantsare acid sensitive) play impor- ARsystems:AR system1 (oxidative,glucose repressed), tantroles in tolerance to organic acids but are of minor ARsystem2 (fermentative,glutamate dependent), and AR importancewith regard to inorganic acid stress (4, 8). The system3 (fermentative,arginine dependent). The system two-componentregulatory system PhoP/ Qprotectsagainst induceddepends on the type of medium and the growth inorganicbut not organic acid stress (8). ThePhoP protein conditions (4). 1298 SMITH J.FoodProt., Vol. 66, No. 7

The ss-dependent,cAMP receptor protein– dependent, Thus,the AR systemsprobably protect cells against gastric andcAMP-dependent glucose-repressed oxidative AR sys- acidityas well as against the volatile fatty acids produced tem(AR system1) is induced when E. coli or S.  exneri bybacteria present in the intestine. cellsare grown to the stationary phase in a glucose-free complexmedium at pH 5.5. These cells survive acid chal- H. pylori and Y.enterocolitica. At leasttwo microor- lengeat pH 2.5 for severalhours in minimal media (4, 16, ganisms, Y.enterocolitica and H. pylori, useurease for sur- 34). Itis not clear how AR system1 protectscells against vivalin the acid stomach. In humans, the metabolic break- acidchallenge. downof proteins leads to ammonia formation. The am- Theglutamate-dependen tARsystem(AR system2) is moniais detoxiŽ ed in the liver via conversion to urea, inducedin cells of E. coli or S.  exneri grownto the sta- whichis secreted into the bloodstream and sequestered by tionaryphase in a glucose-containingcomplex medium at thekidneys and is eventually excreted in urine (109). In- pH5.0. The cells can survive at of 2.0 to 2.5 for dividualswith normal blood urea nitrogen levels have severalhours in minimal media containing glutamate. Of bloodurea and gastric juice urea levels of approximately Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 thethree known AR systems,the glutamate-dependen tAR 4.8and 3.3 mM, respectively (53). Thepresence of ureain systemprovides the highest level of protectionagainst low thestomach is due to its diffusion from theblood circula- pHs (4, 34). torysystem through mucosal tissues into the stomach (105). Theglutamate-dependen tARsystemdepends on the Inthe presence of urea, H. pylori survivedin Mc- inductionof glutamate decarboxylase. During the decar- Ilvain’s bufferat pH 4.0, but survival was poorwhen urea boxylationof glutamate, protons that leak into bacterial was omitted (77). isan essential enzyme in H. py- cellsduring acid stress are taken up toform g-aminobutyric lori. Themajor portion of urease is located intracellularly, acid(GABA). TheGABA istransported out of the cell in with ,0.2%of the enzyme being located at the surface of exchangefor glutamatevia the glutamate:GABA antiporter . the cell (95). Sinceurea is presentin the stomach, it is the TheGABA mechanismfor sequesteringprotons is quite productionof ammonia by urease that allows H. pylori to effectivein preventing the internal pH of the cell from overcomethe acidic conditions and to colonizethe stomach droppingto a lethallevel (4, 16, 34). (34, 105). Urease-negativemutants of H. pylori are unable Thereare three genes necessary for theglutamate de- tocolonize the mouse stomach (32, 111). carboxylasesystem. The genes gadA and gadB encode for Theinner membrane protein UreI isessential for H. highlyhomologous glutamate decarboxylase isoforms, and pylori survivalat low pHs andfor thegastric colonization the gene gadC encodesfor theglutamate:GABA antiporter ofmice.The UreI proteinis anacid-activated urea channel (16). Either gadA or gadB issufŽ cient for thesurvival of thatallows rapid transit (at low pHs) ofexternalurea to the acid-stressedcells at pH 2.5, but both gadA and gadB are intracellularurease of the organism (13). Alowexternal neededfor survivalat pH 2.0. pHstimulates the entry of urea via UreI, therebyleading Thearginine-dependent AR system(AR system3) in- tothe production of ammonia by the urease present in the volvesthe induction of argininedecarboxylase when E. coli cytoplasm.The protons present in the gastric  uiddiffuse cellsare grown to the stationary phase in a glucose-con- into the H. pylori cytoplasmand are bound by ammonia 1 tainingcomplex medium. Such cells are able to survive for (106, 107). Theprotonated ammonia (i.e., NH 4 ) exits the 1 severalhours when challenged in an arginine-supplement ed cellvia an unidentiŽ ed NH 4 exporter.Urease activityin minimalmedium at pH2.5. For ARsystem3, thestructural H. pylori servesto maintain the cytoplasmic pH close to genefor argininedecarboxylase, adiA, andthe regulatory neutralitywhen the organism is exposedto thegastric acid- genes, cysB and adiY, mustbe present (4,16, 34, 60). The ityof the stomach (106, 107). expressionof adiA isactivated by the regulatory protein Inaddition to having the urease system to increaseacid CysB,a globalregulator for sulfurassimilation from inor- resistance, H. pylori hasa urea-independentA TRsystem. ganicsulfate and organic sulfur compounds in E.coli(114). Cellspreexposed to pH 5 orpH 6 were foundto survive Itis notclear why adiA isregulated by CysB.The arginine- exposureto pH 3onehundred times as wellas cellspreex- dependentAR systemacts very much like the glutamate- posedto pH 7 did (52). Theiron uptake regulator Fur is dependentAR system.Intracellular arginine is decarbox- alsoinvolved in acidresistance in H. pylori. Uponexposure ylatedto agmatine, and a protonis taken up during the topH 3.5 or pH 4.8, wild-type H. pylori and fur mutants reaction.The agmatine is transported out of thecell via an of H. pylori showedsimilar rates of survival;however ,the unknownmechanism (34). System3 ARhasnot been dem- growthrate for fur mutantsat pH 5.0 was approximately onstratedfor S.exneri(4). 10-foldlower than that for thewild type (12). Thus, the Oncethe AR systemsare induced in serotype O157: presenceof the fur genedoes not affect the survival of H. H7strains of E. coli (andprobably S.  exneri),theactivity pylori followingacid shock but is necessary for growth willpersist at refrigeration temperatures for atleast 1 month underacid conditions. The involvement of fur inthe growth (60). Theobservation that AR ismaintained for longpe- of H. pylori atacid pHs is ureaseand iron independent (12). riodsduring cold storage has obvious implications with re- Stationary-phase Y.enterocolitica suspendedin pH2.5 spectto foodborne illness. phosphate-bufferedsaline containing 0.1 to 10 mM urea Lin et al. (60) havedemonstrated that AR systems2 survivedthe acid conditions for atleast 2 h.None of the and3 protect E. coli O157:H7against volatile organic acids cellssurvived at pH 2.5 in the absence of urea (24). The suchacetic, butyric, and propionic acids, as well as HCl. rateof recovery of wild-type Y.enterocolitica from theilea J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1299 ofmice receiving an oral inoculum of the organism was ratefor unadaptedcells. In addition, acid-adapted E. coli 100%;however ,therate of recovery of a urease-negative O157:H7survived four times as longas unadaptedcells in mutantfrom miceilea was onlyabout 10% (24). applecider at pH 3.5 stored at 6 8C (58). Theprotection The yut genepresent in Yersiniae speciesencodes the againstthese acidiŽ ed foods observed for E. coli O157:H7 urea-transportingprotein Yut. The mechanism of Yut urea was probablydue to the induction of log-phase A TR. istransported via channel-mediated diffusion. Although Hovde et al. (47) demonstratedthat E. coli O157:H7 theyare structurally unrelated, Yersinia Yut and H. pylori presentin cattle feces were resistantto acidconditions (pH Urel arefunctionally interchangeable (96). Theacid sensi- 2.0, 1 h, 378C). E. coli O157:H7residing in the ruminant tivity of Yersinia resultedwhen the yut genewas inacti- gastrointestinaltract has AR systems1 and2 (4). In a study vated.The insertion of urel into Yersinia orthe insertion involving rpoS mutants of E. coli O157:H7,Price et al. (82) of yut into H. pylori ledto channel-mediated diffusion of found that ss isrequired for therecovery of viable organ- ureainto the bacterial cells (96). Theurease of Y. entero- ismsfollowing passage through the gastrointestinal tracts colitica hasan optimumpH of5.0,with little urease activity ofmice and calves. The need for ss suggeststhe involve- Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 takingplace at neutral pHs. In the acid stomach, the intra- mentof ARsystem1. E. coli O157:H7mutants lacking the cellularurease of Y.enterocolitica maintainsthe cytoplas- gadC genedid not survive passage through the ruminant micpH atca.5.0 through the production of ammoniafrom intestinaltract, indicating that AR system2 isalso neces- urea (95). Aninternal pH of 5.0 is incompatible with saryfor thesurvival of E. coli O157:H7in ruminants (4). growth,and therefore Y.enterocolitica cannotcolonize the However,onlythe ss-dependentAR system1 was required stomachbut can resist the acid conditions and pass into the for thesurvival of E. coli O157:H7in apple cider at pH intestinaltract (95). 3.5, since gadC and adiA mutantssurvived as well as wild- Itis clear that urease action is necessary for thesur- type E. coli O157:H7 did (4). vival of Y.enterocolitica and H. pylori underacid condi- Log-phase L.monocytogenes adaptedto lactic acid at tions.It is urease activity that allows the passage of Y. en- pH5.5 survived longer in yogurt at pH 3.9, in cottage terocolitica throughthe stomach and into the intestinal cheeseat pH 4.7, in orange juice at pH 3.8, and in salad tract.Urease activityis responsible for thesurvival of H. dressingat pH 3.0than unadapted cells did (36). There was pylori survivalin the stomach and for thesubsequent col- noinactivation of acid-adapted L.monocytogenes during onizationof that organ by the organisms. milkfermentation (with a ŽnalpH of 4.2) with the use of alacticstarter culture. The results obtained by Gahanet al. Other bacteria. Otherfoodborne pathogens exhibit the (36) indicatedthat the log-phase A TRsystemprovided pro- inductionof an A TRwhenthey are exposed to mild acid tection for L.monocytogenes presentin acidicfoods. Wild- conditions(ca. pH 5.0) for ashortperiod, with resulting type L.monocytogenes cellsadded to human gastric  uid protectionagainst acid stress at pHs of 3.0 to 3.5. Such (pH 2.5)containing 10 mM glutamate were notkilled by pathogensinclude Aeromonashydrophilia (51), Clostridi- theacid conditions during a 60-mintreatment, whereas in umperfringens (115), L. monocytogenes(75, 76, 80), and theabsence of glutamate, the numbers of wild-type cells V.cholerae(67– 69). Inaddition to having an A TRsystem, were reduced .100-foldin 60 min (21). Mutantslacking L.monocytogenes cellsalso have AR system2, the gluta- gadA and gadB didnot survive gastric acid exposure for matedecarboxylase system. The glutamate decarboxylase 60min whether or not glutamate was present,indicating systemprotects L.monocytogenes againstthe environment thatAR system2 isnecessaryfor thesurvival of L. mono- ofgastric juice at pH 2.5 (21) andagainst the acid envi- cytogenes ingastric  uid (21). Cotteret al. (22) found that ronmentpresent in low-pH foods (22). gadA and gadB were requiredfor thesurvival of L. mono- RELEVANCE OFBACTERIAL cytogenes inacidic foods such as apple juice, orange juice, ACID ADAPTATION tomatojuice, salad dressing, mayonnaise, and yogurt. Thus, theglutamate-dependen tARsystem2 isnecessary to pro- Ithas been reported that the acid-adaptive mechanisms tect L.monocytogenes againstacidic conditions found in employedby bacteria are quite effective in ‘ ‘real-life’’ sit- foodand in the stomach. These reports indicate that acid- uations,which indicates that these mechanisms play a vital adaptivemechanisms are important in the resistance of a rolein the survival of these organisms in acid foods or numberof enteric pathogens to acidic conditions found in duringpassage through the acid stomach. For example, Sal- thestomach and in foods. monella Typhimuriuminduced for log-phaseA TRbyad- CONCLUSIONS aptationto HCl-containing medium (pH 5.8)survived at least10 dayslonger than did unadapted cells in mozzarella, Theproduction of gastric acid by the stomach is an Cheddar,andSwiss cheesesstored at 5 8C (56). efŽcient mechanism for thedestruction of pathogens in- Overnightcultures of E. coli O157:H7kept in nutrient gestedwith food or water .However,anumberof parame- brothat pH 5.0 (acidiŽ ed with HCl) for 4to5 hshowed terscan lead to hypochlorhydria or achlorhydriawith a con- survivalrates that were ca.100-fold higher than those for currentloss of the protective system afforded by gastric unadaptedcells during lactic acid bacterial fermentation of acid. meatto pH 4.4 (58). There was a ;10-foldincrease in the Themanner in which many physicians treat peptic ul- survivalrate for acid-adapted E. coli O157:H7after 4 days cerdisease can cause the protective mechanism of gastric ina hardsalami (pH 5.0)stored at 5 8Ccomparedwith the acidto fail. Since the majority of peptic ulcer disease cases 1300 SMITH J.FoodProt., Vol. 66, No. 7 arecaused by H. pylori, theuse of antibiotics to eliminate 9.Bearson, S., B.Bearson,and J. W.Foster.1997.Acid stress re- thisorganism, rather than treatment with drugs that elimi- sponsesin enterobacter . FEMSMicrobiol.Lett. 147:173–180. 10.Bearson, S. M.D.,W .H.Benjamin,W .E.Swords,and J. W.Foster. nategastric acid secretion or activity, should be the treat- 1996.Acid shock induction of RpoS is mediated bythe mouse mentof choice.The use of antibiotics to eliminatethe ulcer- virulencegene mviA of Salmonellatyphimurium. J. Bacteriol. 178: causingorganisms will put fewer individualsat risk for 2572–2579. food-or waterborne illnesses due to drug treatments that 11.Benjamin, N., F .O’Driscoll,H. Dougall,C. Duncan,L. Smith,M. inducehypochlorhydria. Golden,and H. McKenzie. 1994.Stomach NO synthesis. Nature Entericpathogens do not always have to wait until the 368:502. 12.Bijlsma, J.J.E.,B.Waidner,A.H.M.vanVliet, N. J.Hughes,S. stomachis in an acid-deŽ cient state to causegastroenteritis. Ha¨g,S. Bereswill, D.J.Kelly,C. M.J.E.Vandenbroucke-Grauls, Bacteriahave developed a numberof adaptivemechanisms M.Kist,and J. C.Kunsters.2002. The Helicobacterpylori ho- thatpermit them to survivethe broad range of acidstresses mologueof the ferric uptakeregulator is involvedin acid resistance. theymay encounter in the external environment, in food, Infect.Immun. 70:606–611. orin an animal host. If bacteriaŽ rst adaptto a moderate 13.Bury-Mone ´,S.,S.Skouloubris,A. Labigne,and H. deReuse. 2001. Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 The Helicobacterpylori UreI protein:role in adaptation to acidity acidiccondition, they will be ableto survivemore extreme andidentiŽ cation of residues essential forits activity and for acid acidicenvironments through the induction of adaptive activation. Mol.Microbiol. 42:1021–1034. mechanismsthat lead to acid resistance. These inducible 14.Carter ,A.O.,A. A.Borczyk,J. A.K.Carlson,B. Harvey,J. C. responsesare of medical and applied signiŽ cance because Hockin,M. A.Karmali, C.Krishnan,D. A.Korn,and H. Lior. theability of bacteria to resist extreme acid environments 1987.A severe outbreakof Escherichiacoli O157:H7–associated hemorrhagiccolitis in a nursinghome. N.Engl.J. Med. 317:1496– ensuresthat these acid-resistant pathogens can survive in 1500. nature,in acid foods, and in the acid stomach (85). 15.Cash, R. A.,S. I.Music,J. P.Libonati,M. J.Snyder,R.P.Wenzel, Sincethe gastric acid protective system can fail, it is andR. B.Hornick.1974. Response of man toinfection with Vibrio necessaryfor individualsto practicea goodwater and food cholerae. I.Clinical,serologic, and bacteriologic response to a hygiene.W aterused for drinkingand food preparation knowninoculum. J. Infect.Dis. 129:45–52. shouldbe properly puriŽ ed and chlorinated. Raw foods 16.Castanie-Cornet, M.-P .,T.A.Penfound,D. Smith,J. F.Elliott,and J.W.Foster.1999.Control of acid resistance in Escherichiacoli. shouldbe obtained from asafe sourceand should then be J. Bacteriol. 181:3525–3535. properlyhandled and stored. Foods must be prepared and 17.Cheng, H.-Y .,H.-Y.Yang,and C.-C. Chou. 2002. In uence ofacid cookedin an appropriate manner and served properly (i.e., adaptationon the tolerance of Escherichiacoli O157:H7to some hotfoods should be servedpromptly and cold foods should subsequentstresses. J.FoodProt. 65:260–265. bekept refrigerated until they are served). Procedures for 18.Clarkston, W .K.,M.M.Pantano,J. E.Morley,M. Horowitz,J. M.LittleŽeld, and F .R.Burton.1997. Evidence for the anorexia thesafe handlingof foodsare given in Smith (103). Above ofaging: gastrointestinal transit and hunger in healthy elderly vs. all,a highdegree of personalcleanliness must be observed. youngadults. Am.J. Physiol. 272:R243–R248. Handsshould be washed with soap and hot water before 19.Cobb, C. A.,G. D.W.Curtis,D. S.Bansi,E. Slade,W .Mehal,R. foodsare prepared and at intervals during the preparation, G.Mitchell,and R. W.Chapman.1996. Increased prevalence of cooking,and serving of foods. Hand washing is the most Listeriamonocytogenes inthe faeces ofpatients receiving long- term H2-antagonists. Eur.J. Gastroenterol.Hepatol. 8:1071–1074. effectivemeans of preventing foodborne disease (110). 20.Cook, G. C.1985.Infective gastroenteritis and its relationship to REFERENCES reducedgastric acidity. Scand.J. Gastroenterol.Suppl. 111:17–23. 21.Cotter ,P.D.,C.G.M.Gahan,and C. Hill.2001. A glutamate 1.Andreoli, T .E.,J. C.Bennett,C. C.J.Carpenter,and F .Plum.1997. decarboxylasesystem protects Listeriamonocytogenes in gastric Cecil essentials ofmedicine, 4th ed., p. 288– 298. W .B.Saunders  uid. Mol.Microbiol. 40:465–475. Co.,Philadelphia. 22.Cotter ,P.D.,K.O’Reilly,and C. Hill.2001. Role of the glutamate 2.Archer ,D.L.2002.Evidence that ingested nitrate and nitrite are decarboxylaseacid resistance system inthe survival of Listeria beneŽcial tohealth. J.FoodProt. 65:872–875. monocytogenes LO28in low pH foods. J. FoodProt. 64:1362– 3.Arnold, K. W.,andC. W.Kaspar.1995.Starvation and stationary- 1368. phase-inducedacid tolerance in Escherichiacoli O157:H7. Appl. 23.de Boer ,W.A.,andG. N.J.Tytgat.2000. Treatment of Helico- Environ.Microbiol. 61:2037–2039. bacterpylori. Br. Med. J. 320:31–34. 4.Audia, J. P.,C.C.Webb,and J. W.Foster.2001.Breaking through 24.de Koning-Ward, T .F.,andR. M.Robins-Brown.1995. Contribu- theacid barrier:an orchestrated response to protonstress byenteric tionof urease toacid tolerance in Yersiniaenterocolitica. Infect. bacteria. Int.J. Med.Microbiol. 291:97–106. Immun. 63:3790–3795. 5.Bang, I. S.,J.P.Audia,Y .K.Park,and J. W.Foster.2002.Au- 25.Doglioni, C., M.deBonio, R. Cielo,L. Laurino,P .Pelosio,P . toinductionof the ompR responseregulator by acid shockand con- Braidotti,and G. Viale. 1992.Gastric giardiasis. J.Clin.Pathol. trol of the Salmonellaenterica acid tolerance response. Mol. Mi- 45:964–967. crobiol. 44:1235–1250. 26.Dressman, J.B.,R. R.Berardi,L. C.Dermentzoglou,T .L.Russell, 6.Bang, I. S.,B.H.Kim, J.W.Foster,andY .K.Park.2000. OmpR S.P.Schmaltz,J. L.Barnett,and K. M.Jarvenpaa.1990. Upper regulatesthe stationary phase acid tolerance responseof Salmonella gastrointestinal(GI) pHinyoung, healthy men andwomen. Pharm. enterica serovarTyphimurium. J.Bacteriol. 182:2245–2252. Res. 7:756–761. 7.Bass, D.M.,andH. B.Greenberg.1995. Group A rotaviruses,p. 27.Drouault, S., G. Corthier,S. D.Ehrlich,and P .Renault.1999. Sur- 967–982. In M.J.Blaser,P.D.Smith,J. J.Ravdin,H. B.Green- vival,physiology, and lysis of Lactococcuslactis inthe digestive berg,and R. L.Guerrant(ed.), Infections of the . Appl.Environ. Microbiol. 65:4881–4886. tract. RavenPress, New York. 28.Duncan, C., H. Dougall,P .Johnston,S. Green, R.Brogan,C. Lei- 8.Bearson, B. L.,L. Wilson,and J. W.Foster.1998. A lowpH- fert,L. Smith,M. Golden,and N. Benjamin.1995 Chemical gen- inducible,PhoPQ-dependent acid tolerance responseprotects Sal- erationof nitric oxide in the mouth from the enterosalivary circu- monellatyphimurium againstinorganic acid stress. J.Bacteriol. lationof dietarynitrate. Nat. Med. 1:546–551. 180:2409–2417. 29.Duncan, D., H. Li,R. Dykhuizen,R. Frazer, P.Johnston,G. J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1301

MacKnight,L. Smith,K. Lamza, H.McKenzie, L.Batt,D. Kelly, 50.Kapikian, A. Z.1997.Viral gastroenteritis,p. 285– 343. In A. S. M.Goldern,N. Benjamin,and C. Leifert.1997. Protection against Evansand R. A.Kaslow (ed.),Viral infectionsof humans: epide- oraland gastrointestinal diseases: importanceof dietary nitrate in- miologyand control, 4th ed. Plenum Medical Book Co., New York. take,oral nitrate reduction and enterosalivary nitrate circulation. 51.Karem, K.L.,J.W.Foster,and A. K.Bej.1994. Adaptive acid Comp.Biochem. Physiol. 118A:939–948. tolerance response(ATR) in Aeromonashydrophilia. Microbiology 30.Dundas, S., W.T.A.Todd,A. I.Stewart,P .S.Murdoch,A. K.R. 140:1731–1736. Chaudhuri,and S. J.Hutchinson.2001. The central Scotland Esch- 52.Karita, M.,andM. J.Blaser.1998.Acid-tolerance response in Hel- erichiacoli O157:H7outbreak: risk factors forthe hemolytic ure- icobacterpylori anddifferences between cagA1 and cagA2 strains. mic syndromeand death among hospitalized patients. Clin.Infect. J. Infect.Dis. 178:213–219. Dis. 33:923–931. 53.Kim, H.,C. Park,W .I.Jang,K. H.Lee, S.O.Kwon,S. S.Robey- 31.Dykhuizen, R., R.Frazier,C.Duncan,C. C.Smith,M. Golden,N. Cafferty,J. Y.Ro,and Y .B.Lee. 1990.The gastric juiceurea and Benjamin,and C. Leifert.1996. Antimicrobial effect ofacidiŽ ed ammonia levels inpatients with Campylobacterpylori. Am. J. Clin. nitriteon gut pathogens: importance of dietary nitrate in host de- Pathol. 94:187–191. fense. Antimicrob.Agents Chemother. 40:1422–1425. 54.Koo, J., A. DePaola,and D. L.Marshall.2000. Effect ofstimulated

32.Eaton, K. A.,J.V.Gilbert,E. A.Joyce,A. E.Wanken,T .Thevenot, gastric uidand on survival of VibriovulniŽ cus and Vibrio Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 P.Baker,A. Plaut,and A. Wright.2002. In vivo complementation vulniŽ cus phage. J.FoodProt. 63:1665–1669. of UreB restores theability of Helicobacterpylori tocolonize. In- 55.Labenz, J. 2001.Current role of acid suppressantsin Helicobacter fect. Immun. 70:771–778. pylori eradicationtherapy. Best Pract.Res. Clin.Gastroenterol. 15: 33.El-Omar, E.M.,M.Carrington,W .-H.Chow, K. E.L.McColl,J. 413–431. H.Bream, H.A.Young,J. Herrera, J.Lissowska,C.-C. Y uan,N. 56.Leyer, G. J.,and E. A.Johnson.1992. Acid adaptation promotes Rothman,G. Lanyon,M. Maartin,J. F.Fraument,and C. S.Rabkin. survival of Salmonella spp.in cheese. Appl.Environ. Microbiol. 2000.Interleukin-1 polymorphisms associated withincreased risk 58:2075–2080. ofgastric cancer. Nature 404:398–402. 57.Leyer, G. J.,and E. A.Johnson.1993. Acid adaptation induces 34.Foster ,J.W.2000.Microbial responses to acid stress, p.99– 115. cross-protectionagainst environmental stresses in Salmonellaty- In G.Storzand R. Hengge-Aronis(ed.), Bacterial stress responses. phimurium.Appl. Environ. Microbiol. 59:1842–1847. ASMPress, Washington,D.C. 58.Leyer, G. J.,L.-L. Wang, and E. A.Johnson.1995. Acid adaptation 35.Gahan, C. G.M.,andC. Hill.1999. The relationship between acid of Escherichiacoli O157:H7increases survivalin acidic foods. stress responsesand virulence in Salmonellatyphimurium and Lis- Appl.Environ. Microbiol. 61:3752–3755. teriamonocytogenes. Int. J. FoodMicrobiol. 50:93–100. 59.Lin, J., I. S.Lee, J.Frey,J. L.Slonczewski,and J. W.Foster.1995. 36.Gahan, C. G.M.,B.O’Driscoll,and C. Hill.1996. Acid adaptation Comparativeanalysis of extreme acid survivalin Salmonellaty- of Listeriamonocytogenes can enhancesurvival in acidic foodsand phimurium,Shigella  exneri, and Escherichiacoli. J. Bacteriol. duringmilk fermentations. Appl.Environ. Microbiol. 62:3128– 177:4097–4104. 3132. 60.Lin, J., M. P.Smith,K. C.Chapin,H. S.Baik,G. N.Bennett,and 37.Giannella, R. A.,S. A.Broitman,and N. Zamcheck. 1972.Gastric J.W.Foster.1996. Mechanism ofacid resistance inenterohemor- acid barrier toingested in man: studiesin vivo and rhagic Escherichiacoli. Appl. Environ. Microbiol. 62:3094–3100. in vitro. Gut 13:251–256. 61.Lloyd, R. C.K.,andH. T.Debas. 1994.Peripheral regulation of 38.Gitelson, S. 1971.Gastrectomy, achlorhydriaand . Isr. J. gastric acid secretion,p. 1185– 1226. In L.R.Johnson,D. H.Al- Med. Sci. 7:663–667. pers,J. Christensen,E. D.Jacobson,and J. H.Walsh(ed.), Phys- 39.Glupczynski, Y .1998.Infection with Helicobacter, p. 581–591. In iologyof the gastrointestinal tract, 3rded., vol. 2. Raven Press, L.Collier(ed.), T opley& Wilson’s microbiologyand microbiolog- New York. ical infections,9th ed., vol. 3. Arnold, London. 62.Lund, B. M.,andT .Eklund.2000. Control of pHanduse oforganic 40.Goodson, M., andR. J.Rowbury. 1989. Habituation to normally acids,p. 175– 199. In B.M.Lund,T .C.Baird-Parker,andG. W. lethalacidity by prior growth of Escherichiacoli at asub-lethal Gould(ed.), The microbiological safety andquality of food,vol. 1. acid pHvalue. Lett.Appl. Microbiol. 8:77–79. AspenPublishers, Gaithersburg, Md. 41.Graff, J.,K. Brinch,and J. L.Madsen.2001. Gastrointestinal mean 63.Marciani, L., P.A.Gowland,R. C.Spiller,P.Manoj,R. J.Moore, transittimes inyoung and middle-aged healthy subjects. Clin. Phy- P.Young,and A. J.Fillery-Travis.2001. Effect ofmeal viscosity siol. 21:253–259. andnutrients on satiety, intragastric dilution, and emptying assessed 42.Helander ,H.F.,andD. J.Keeling.1993. Cell biologyof gastric by MRI. Am.J. Physiol.Gastrointest. Liver Physiol. 280:G1227– acid secretion. Baillie`res Clin.Gastroenterol. 7:1–21. G1233. 43.Ho, J. L.,K.N.Shands,G. Friedland,P .Eckind,and D. W.Fraser. 64.McKnight, G. M.,C.W.Duncan,C. Liefert,and M. H.Golden. 1986.An outbreak of type 4b Listeriamonocytogenes infection 1999.Dietary nitratein man: friendor foe? Br. J. Nutr. 81:349– involvingpatients from eight Boston hospitals. Arch.Intern. Med. 358. 146:520–524. 65.Mead, P .S.,L.Slutsker,V.Dietz, L.F.McCaig,J. S.Bresee, C. 44.Holt, P .1985.Severe Salmonella infectionin patientswith reduced Shapiro,P .M.GrifŽn, and R. V.Tauxe.1999. Food-related illness gastric acidity. Practitioner 229:1027–1028, 1030. anddeath in the United States. Emerg.Infect. Dis. 5:607–625. 45.Holtmann, G., andN. J.Talley.1995. Clinical approach to the Hel- 66.Merck Research Laboratories.1992. Merck Manual of Diagnosis icobacter patient,p. 565– 587. In M.J.Blaser, P.D.Smith,J. I. andTherapy, 16th ed., p. 770.Merck Research Laboratories,Rah- Ravdin,H. B.Greenberg,and R. L.Guerrant(ed.), Infection of the way, N.J. gastrointestinaltract. RavenPress, New York. 67.Merrell, D. S.,C.Bailelly,J. B.Kaper,andA. Camilli.2001. The 46.Hornick, R. B.,S.J.Music,R. Wenzel, R.Cash,J. P.Libonati,M. ToxR-mediatedorganic acid tolerance responseof Vibriocholerae J.Snyder,and T .E.Woodward.1971. The Broad Street pumpre- requiresOmpU. J.Bacteriol. 183:2746–2754. visited:response of volunteers to ingested cholera vibrios. Bull. 68.Merrell, D. S.,andA. Camilli.1999. The cadA gene of Vibrio N.Y.Acad. Med. 47:1181–1191. cholerae is inducedduring infection and plays a rolein acid tol- 47.Hovde, C. J.,P .R.Austin,K. A.Cloud,C. J.Williams,and C. W. erance. Mol.Microbiol. 34:836–849. Hunt.1999. Effect ofcattle dieton Escherichiacoli O157:H7acid 69.Merrell, D. S.,and A. Camilli.2000. Regulation of Vibriocholerae resistance. Appl.Environ. Microbiol. 65:3233–3235. genesrequired for acid tolerance bya member ofthe ‘ ‘ToxR-like’’ 48.Howden, C. W.,andR. H.Hunt.1987. Relationship between gastric familyof transcriptionalregulators. J.Bacteriol. 182:5342–5350. secretionand infection. Gut 28:96–107. 70.Nalin, D. E.,M. M.Levine,J. Rhead,E. Bergquist,M. Rennels, 49.Johnson, L. R.2001.Gastric secretion,p. 75–94. In L.R.Johnson T.Hughes,S. O’Donnell,and R. B.Hornick.1978. Cannabis, hy- (ed.),Gastrointestinal physiology, 6th ed. Mosby, St. Louis, Mo. pochlorhydria,and cholera. Lancet ii:859–862. 1302 SMITH J.FoodProt., Vol. 66, No. 7

71.Nalin, D. R.,R. J.Levine,M. M.Levine,D. Hoover,E.Bergquist, 91.Sanad, M. M.,R.A.Darwish,M. E.Nasr,N.E.El-Gammal, and J.McLaughlin,J. Libonati,J. Alam, andR. B.Hornick.1978. Chol- M.W.Emara. 1996. Giardialamblia andchronic gastritis. J. Egypt. era, non-vibriocholera, and stomach acid. Lancet ii:856–859. Soc.Parasitol. 26:481–495. 72.Neal, R.K.,O. S.Brij,B. C.R.Slack,J. E.Hawkey,and R. F.A. 92.Schiraldi, O., V .Benvestito,C. diBari,R. Moschetta,and G. Pas- Logan.1994. Recent treatment withH2 antagonists and antibiotics tore.1974. Gastric abnormalitiesin cholera: epidemiological and andgastric surgeryas riskfactors for Salmonella infection. Br. clinicalconsiderations. Bull.World Health Organ. 51:349–352. Med. J. 308:176. 93.Schlech, W .F.,D.P.Chase, andA. Badley.1993. A modelof food- 73.Neal, R.K.,H.M.Scott,R. C.Slack,and R. R.A.Logan.1996. borne Listeriamonocytogenes infectionin the Sprague-Dawley rat Omeprazole as ariskfactor for Campylobacter gastroenteritis:case- usinggastric inoculation:development and effect ofgastric acidity controlstudy. Br. Med. J. 312:414–415. oninfective dose. Int.J. FoodMicrobiol. 18:15–24. 74.Nordbring, F .1962.Contraction of Salmonella gastroenteritisfol- 94.Scholz, E., U.Heinricy,and B. Flehmig.1989. Acid stability of lowingprevious operation on the stomach. ActaMed. Scand. 171: hepatitisA virus. J.Gen.Virol. 70:2481–2485. 783–790. 95.Scott, D. R.,E.A.Marcus,D. L.Weeks,and G. Sachs.2002. 75.O’ Driscoll,B., C.G.M.Gahan,and C. Hill.1996. Adaptive acid Mechanisms ofacid resistance dueto the urease system of Heli-

tolerance responsein Listeriamonocytogenes :isolationof anacid- cobacterpylori. 123:187–195. Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 tolerantmutant which demonstrates increased virulence. Appl. En- 96.Sebbane, F .,S.Bury-Mone´,K.Cailliau,E. Browadys-Poly,H. de viron.Microbiol. 62:1693–1698. Reuse, andM. Simonet.2002. The Yersiniapseudotuberculosis Yut 76.O’ Driscoll,B., C.G.M.Gahan,and C. Hill.1997. Two-dimen- protein,a new typeof urea transporterhomologous to eukaryotic sionalpolyacrylamide gel electrophoresis analysis of the acid tol- channelsand functionally interchangeable in vitro with the Heli- erance responsein Listeriamonocytogenes LO28. Appl.Environ. cobacter Urel protein. Mol.Microbiol. 45:1165–1174. Microbiol. 63:2679–2685. 97.Sehic, E., S. Li,A. L.Ungar,and C. M.Blatteis.1998. Complement 77.Pe ´rez-Pe´rez, G.L.,A.Z.Olivares,T .L.Cover,andM. Blaser. reductionimpairs thefebrile response of guineapigs to endotoxin. 1992.Characteristics of Helicobacterpylori variantsselected for Am.J. Physiol. 274:R1594–R1603. urease deŽciency. Infect.Immun. 60:3658–3663. 98.Shamburek, R. D.,and M. L.Schubert.1992. Control of gastric 78.Pertwee, R.G.2001.Cannabinoids and the gastrointestinal tract. 1 1 acid secretion.Histamine H 2-receptorantagonists and H K - Gut 48:859–867. ATPase inhibitors. Gastroenterol.Clin. North Am. 21:527–550. 79.Peterson, W .L.,P .A.Mackowiak,C. A.Barnett,M. Marling-Ca- 99.Shamburek, R. D.,and M. L.Schubert.1993. Pharmacology of son,and M. L.Haley.1989. The human gastric bactericidal barrier: gastric acid secretion. Baillie`res Clin.Gastroenterol. 7:23–54. mechanisms ofaction,relative antibacterialactivity and dietary in- 100.Sherman, P .M.,andS. N.Lichtman.1995. Pediatric considerations  uences. J. Infect.Dis. 159:979–983. relevantto enteric infections,p. 143– 152. In M.J.Blaser,P.D. 80.Phan-Thanh, L., F .Mahouin,and S. Alige´.2000.Acid responses Smith,J. J.Ravdin,H. B.Greenberg,and R. L.Guerrant(ed.), of Listeriamonocytogenes. Int. J. FoodMicrobiol. 55:121–126. Infectionsof the gastrointestinal tract. RavenPress, New York. 81.Pickering, L. K.,R.L.Guerrant,and T .G.Cleary.1995. Micro- 101.Smith, J. L.1991.Foodborne toxoplasmosis. J. Food Saf. 12:17– organismsresponsible for neonatal diarrhea, p. 1142– 1222. In J. S. 57. Remingtonand J. O.Klein(ed.), Infectious diseases ofthe fetus 102.Smith, J. L.1998.Foodborne illness in the elderly. J.FoodProt. andnewborn infant, 4th ed. W .B.Saunders,Philadelphia. 61:1229–1239. 82.Price, S. B.,C.-M.Cheng, C. W.Kaspar,J.C.Wright,F .J.De- 103.Smith, J. L.1999.Foodborne infections during pregnancy. J. Food Graves, T.A.Penfound,M.-P .Castanie-Cornet,and J. W.Foster. Prot. 62:818–829. 2000.Role of rpoS inacid resistance andfecal sheddingof Esch- 104.Soll, A. H.,and T .Berglindh.1994. Receptors thatregulate gastric erichiacoli O157:H7. Appl.Environ. Microbiol. 66:632–637. acid-secretory function,p. 1139 –1169. In L.R.Johnson,D. H. 83.Roering, A. M.,J. B.Luchansky,A. M.Ihnot,S. E.Ansay,C. W. Alpers,J. Christensen,E. D.Jacobson,and J. H.Walsh(ed.), Phys- Kaspar,andS. C.Ingham.1999. Comparative survival of Salmo- iologyof the gastrointestinal tract, 3rded., vol. 2. Raven Press, nellatyphimurium DT 104, Listeriamonocytogenes, and Esche- New York. richia coli O157:H7in preservative-free applecider andsimulated gastric uid. Int.J. FoodMicrobiol. 46:263–269. 105.Stanton, T .2000.Ecological aspects ofhostcolonization: coaggre- 84.Rotker, J. D.,A.Strapko,J. Nandi,M. C.Bosche,and R. A.Levine. gation,osmoadaptation, and acid tolerance orresistance, p.61– 75. 1995.Effects ofcyclic adenosinemonophosphate-dependent pro- In K.A.Brogden,J. A.Roth,T .B.Stanton,C. A.Bolink,F .C. teinkinase and calcium-dependent protein kinase modulators on Minion,and M. J.Wannemuehler(ed.), Virulence mechanisms of stimulatedgastric glandsecretion in the perfused rat stomach. bacterial pathogens.ASM Press, Washington,D.C. Pharmacology 51:263–272. 106.Stingl, K., K. Altendorf,and E. P.Bakker.2002. Acid survival of 85.Rowbury, R. J.,andM. Goodson.1998. Glucose-induced acid tol- Helicobacterpylori :howdoes urease activitytrigger cytoplasmic erance appearingat neutralpH in log-phase Escherichiacoli and pHhomeostasis? TrendsMicrobiol. 10:70–74. itsreversal bycyclic AMP. J.Appl.Microbiol. 85:615–620. 107.Stingl, K., E.-M.Uhlemann, R. Schmid,K. Altendorf,and E. P. 86.Russell, T .L.,R.R.Beradi,J. L.Barnett,L. C.Dermentzoglou,K. Bakker.2002.Energetics of Helicobacterpylori andits implications M.Jarvenpaa,S. P.Schmaltz,and J. B.Dressmen. 1993.Upper forthe mechanism ofurease-dependent acid tolerance at pH1. J. gastrointestinalpH in seventy-nine healthy, elderly, North Ameri- Bacteriol. 184:3053–3060. can men andwomen. Pharm. Res. 10:187–196. 108.T akumi,K., R.deJonge, and A. Havelaar. 2000.Modelling inac- 87.Sachs, G. 1994.The gastric H,KATPase, p.1119 –1138. In L. R. tivation of Escherichiacoli bylow pH: application to passage Johnson,D. H.Alpers,J. Christensen,E. D.Jacobson,and J. H. throughthe stomach ofyoung and elderly people. J.Appl.Micro- Walsh(ed.), Physiology of the gastrointestinal tract, 3rded., vol. biol. 89:935–943. 2.Raven Press, New York. 109.T arver,H. 1951.The metabolism ofamino acids andproteins, p. 88.Sachs, G., C. Prinz,D. Loo,K. Bamberg,M. Besancon,and J. M. 769–908. In D.M.Greenberg(ed.), Amino acids andproteins: Shin.1994. Gastric acid secretion:activation and inhibition. Yale theory,methods, applications. Charles CThomas,SpringŽ eld, Ill. J. Biol.Med. 67:81–95. 110.T aylor,A.K.2000.Food protection: new developmentsin hand- 89.Sachs, G., J. M.Shin,C. Briving,B. Wallmark,and S. Hersey. washing. Dairy FoodEnviron. Sanit. 20:114–119. 1995.The pharmacology of the gastric acid pump:the H 1,K1 111.Tsuda, M., M.Karita, M.G.Morshed,K. Okita,and T .Nakazawa. ATPase. Annu.Rev. Pharmacol.Toxicol. 35:277–305. 1994.A urease-negativemutant of Helicobacterpylori constructed 90.Sack, G. H.,N.F.Pierce, K.N.Hennessey,R. C.Mitra,R. B. byallelic exchangemutagenesis lacks theability to colonize the Sack,and D. N.G.Mazumder.1972. Gastric acidityin cholera and nudemouse stomach. Infect.Immun. 62:3586–3589. noncholeradiarrhoea. Bull.World Health Organ. 47:31–36. 112.Urushidani, T .,andJ. G.Forte.1997. Signal transduction and ac- J.FoodProt., Vol. 66, No. 7 EFFECTOF GASTRICACID ONFOODBORNE PATHOGENS 1303

tivationof acid secretionin the parietal cell. J.Membr.Biol. 159: pathogensare protectedfrom killing under extremely acidic con- 99–111. ditionsof pH2.5when they are inoculatedonto certain solidfood 113.V alle, J.D.,H. Cohen,L. Laine,and J. M. Scheiman.1999. Acid sources. Appl.Environ. Microbiol. 64:3882–3886. pepticdisorders, p. 1370 –1444. In T.Yamada (ed.),Textbook of 118.W eaver, L.T.,A.J.Shepherd,C. P.Doherty,K. E.L.McColl,and gastroenterology,3rd ed., vol. 1. Lippincott Williams &Wilkins, C.L.Williams.1999. Helicobacterpylori inthe faeces? Q. J. Med. Philadelphia. 92:361–364. 114.van der Ploeg, J. R., E. Eichhorn,and T .Leisinger.2001.Sulfonate- 119.W eiss, C.,andH. F.Clark.1985. Rapid inactivation of rotaviruses sulfurmetabolism andits regulation in Escherichiacoli. Arch. Mi- byexposure to acid bufferor acidic gastric juice. J. Gen.Virol. 66: crobiol. 176:1–8. 2725–2730. 115.Villarreal, L.,N.L.Heredia, andS. Garc ´‡a. 2000.Changes in pro- 120.Xu, J., X. Xu,and W .Verstraete. 2001.The bactericidal effect and teinsynthesis and acid tolerance in Clostridiumperfringens type A chemical reactionsof acidiŽ ed nitrite under conditions simulating inresponse to acid shock. Int.Microbiol. 3:113–116. thestomach. J.Appl.Microbiol. 90:523–529. 116.W addell,W .R.,and L. J.Kunz.1956. Association of salmonella 121.Y ardley,J. H.,and T .R.Hendrix.1999. Gastritis, gastropathy, du- enteritiswith operations on thestomach. N.Engl.J. Med. 255:555– odenitis,and associated ulcerativelesions, p. 1463–1499. In T. Ya-

359. mada (ed.),Textbook of gastroenterology, 3rd ed., vol. 1. Lippincott Downloaded from http://meridian.allenpress.com/jfp/article-pdf/66/7/1292/1672711/0362-028x-66_7_1292.pdf by guest on 30 September 2021 117.W aterman, S.R.,andP .L.C.Small.1998. Acid-sensitive enteric Williams &Wilkins,Philadelphia.

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