Gram-positive : and corynebacteria

Katedra i Zakład Mikrobiologii UM Wrocław Important terms

.lysogenic bacteria .anatoxine - .active immunization .passive immunization .zoonosis Important terms - lysogenic bacteria

Lysogenic bacteria - bacteria that is infected with a temporate bacteriophage and bacteriophage’s DNA is integrated into the bacteria's chromosome (viral genes are present in the bacterium without causing disruption of the bacterial cell)

Important terms - anatoxine

TOXIN TOXOID

Toxicity Toxicity anatoxine = toxoid - bacterial toxinAntigenicity whose toxicity hasAntigenicity been weakened or suppressed; can be used for safe active immunization

Convertion : - heat Stimule active immunity - chemicals (toxoid vacines) Important terms – active immunization

inactivated/killed pathogen non-virulent or attenuated pathogen Bacterial proteins or polysaccharides (Subunit/conjugate) toxoid active immunization - stimulation with a specific antigen to promote formation in the body. Protection against disease may last several years, in some cases for life Important terms - passive immunization

Passive immunity - providing IgG to protect against (immediate, but short- lived protection) : a) natural - maternal antibody (mainly IgG) protect the newborn baby b) acquired passive immunity - process of obtaining serum from immune individuals, andacquired then injecting it to protectnatural a susceptible person. Important terms - zoonosis

zoonosis is any disease or that is naturally transmissible from vertebrate animals to humans as a result of direct or indirect contact with animal population gram positive bacteria

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Clostridium Corynebacterium Erysipelothrix bacilli

(endo)spores sporulation Family: Bacillaceae

Genus: Genus: Bacillus - strict anaerobes - diversity of anaerobic fermentation - facultative or obligate aerobes - variety of extracellular enzymes - many produce (biodegradation & invasive infection)

- - Clostridium tetani - - - - Clostidium difficile

zoonosis disease

capsule causative agent: Bacillus anthracis reservoir: environment, farm animals habitat: GIT of animals Bacillus anthracis complex

LF PA EF main forms of anthrax infection

CUTANEOUS ANTHRAX Transmission: Inoculation inhalation septic shock ingestion INHALATION ANTHRAX (pulmonary anthrax) multiple organ failure

GASTROINTESTINAL ANTHRAX ANTHRAX

therapy: .antibiotics (penicillin, , quinolones) .administered before the onset of lymphatic spread ! prevention: .vaccination of animals (Pasteur 1881) .burning of burial of animals that died of anthrax .possible vaccination for „risk” groups Anthrax is a bioweapon

SYMPTOM FLU ANTHRAX

Sore throat Common Occasional

Runny nose Y N

Fever and chills Y Y

Cough, productive Y N

Cough, dry, unproductive Y Y

Schortness of breath Rare Common

Chest pain rare common Bacillus cereus

Reservoir: environment Habitat: environment Transmission: food-borne, inoculation Bacillus cereus infections

Intravenus Occular infections Catheter (cereolysine) related sepsis GIT

Emetic form Diarrheal form

Heat-stable Heat-labile enterotoxine Proteolysis resistant (meat, vegetables) (Rice)

intoxication toxico infection (gastroenteritis) caused by toxin producing in vivo

Clostridium botulinum lethal dose 0,09 to 0,15 µg intravenously reservoir: environment 0,70 to 0, 90 µg inhaled 70 µg orally Descending paralysis flaccid bilateral cranial neuropathies associated with

symmetric descending weakness

Botulinum muscle paralysis toxin prevent the release of acetylcholine, which stops muscle cells from contracting CLASSIC BOTULISM WOUND BOTULISM INFANT BOTULISM

TOXINE PRODUCED

extrinsically intrinsically incubation period -> from 6 hours to 8 -10 days Inhalational botulism does not occur naturally but would result from breathing in toxin used as a biological weapon

Iatrogenic botulism - occur due to accidental injection into the blood stream of commercial specific treatment of botulism

• Antitoxin – trivalent horse (A, B, E) • Antibiotics ( toxicoinfection) • Supportive measures (mechanical ventilation) entry points: Clostridium tetani .cuts and wounds .burns reservoir: environment, animals, human .animal bites habitat: GIT of animals and humans .intravenous drug use .body piercing and tattoos .circumcision

Transmission: inoculation incubation period :4 to 21 days sardonic smile lockjaw opisthotonus

clinical forms: .generalized .local .neonatal .cephalic

complications of tetanus .bone fractures .aspiration pneumonia .tetanic seizures . death

opisthotonus in tetanus tetanus

Treatment supportive care Prevention: antitoxin vaccination antibiotics Clostridium perfringens

flesh-eating bacterium Reservoir: environment, animals , human Habitat: GIT of animals and humans Transmission: inoculation Pathogenesis

Exogenic infection: Endogenic infection: penetrating wound contaminated after gut rupture, septic abortion with spores (rare) foodborne Clostridium perfringens

After: - gut rupture - septic abortion

Gastrointestinal (GI) SOFT TISSUE INFECTIONS diseases

SEPSIS

MYONECROSIS NECROTIZING toxin produced CELLULITIS ENTERITIS in vivo (GASTROENTERITIS) FASCIITIS Myonecrosis

soft tissue infections with clostidia are typically polymicrobial :

Cl. perfringens (10-48h) Cl. septicum (2-3 days) Cl. histolyticum (3-6 days) Cl. novyi (5-6 days)

Incubation period in : 1-7 days

Clostridium perfringens pathogenesis

EXOTOXINS: Known 12 DEGRADATIVE (α,β,γ,δ,ε etc.) ENZYMES ENTEROTOXIN:

- Heat-labile protein toxin α = lecithinase - leading tp loss of fluid and proteins Proteases

Role: Dnases Role: Hyaluronidase

A) MASIVE LYSIS OF: : collagenases endothelial cells, erythrocytes Leukocytes,platelets Pathogenesis in gastroenteritis Role: B) INCREASED VASCULAR PERMEABILITY a) LIQUEFY TISSUE C) HEPATIC TOXITI, b) PROMOTE THE SPREAD MYOCARDIAL DYSFUNCTION OF INFECTION attention !

Microscopic examination of necrotic tissue reveals: gram-positive bacilli in the absence of inflemmatory cells, which is the result of lysis by clostridial Produces Beta toxine responsible for: - intestinal stasis - loss of mucosa with formation of necrotic lesions Produces ENTEROTOXIN

Cl. perfringens type : A B C D E

All produces α exotoxine

Produces the bigest amount of α TOXINE Cl.perfringens Necrotizing enteritis (Pig-bel disease)

- β toxin produced by Cl. perfringens type C

- Toxine can be inactivated by trypsin BUT: Groups of risk: Papua New Guinea inhabitants (sweet patatoes) population with malnutration

- presentation: acute abdominal pain, ulceration of small intestine, bloody diarrhea perforation of the intestinal wall septic shock

Clostridium difficile

Reservoir: environment, human Habitat: GIT of humans Transmission: Food-borne, endogenous

• AAD (- Associated Diarrheas)

• PMC (Pseudomembranous Colitis) Most common antimicrobial drugs associated with C.difficile diarrhea

• Cephalosporins • Ampicillin • Clostridium difficile

Endogenous source: Broad spectrum antibiotics alters the normal enteric flora

Exogenous source: The hospitalized patients are more susceptible to the exogenous aquisition of C. difficile – nosocomial infection

Cl. difficile pathogenesis

Toxin A enterotoxin that causes fluid accumulation stimulates an inflammantory response

Toxin B potent cytotoxin (distrupts protein synthesis)

Treatment

• withdraw / replace antibiotics

• Oral administration of metronidazole or vancomycin

• Avoid: antidiarrheal agents( prevent colonic stasis)

• Volume resuscitation for dehydrated patients

Coryneforms = diphtheroids

- Pleomorphic rods - Form clumps that Natural human look like Chinese characters flora of: - skin - upper respiratory tract - urogenital tract -

strict pathogens: .lysogenic Corynebacterium diphtheriae .Corynebacterium ulcerans (zoonosis)

Diphtheria - Corynebacterium diphtheriae

•incubation period is 2–5 days but occasionally longer

•humans are the only reservoir

•The disease has now reached endemic status (less developed countries with unvaccinated or partially vaccinated citizens )

•Diphtheria is a disease that must be notified immediately DIPHTHERIA

Upper RESPIRATORY tract infection CUTANEOUS diphtheria is synthesized only by lysogenic bacteria under conditions of iron deficiency.

Diphtheria should be considered:

- In unvaccinated patients with pharyngitis - low grade fever - cervical adenopathy - adherent gray exudate in throat

EXOTOXINE of Corynebacterium diphtheriae

A-B type of toxine A B

A -ctive fragment of toxine B - ind toxine to the receptor & (Inhibits synthesis of human mediates delivery A to its target proteins) Fragment A catalyzes the transfer of ADP-ribose from NAD to the eucaryotic Elongation Factor 2 which inhibits the function of the latter in protein synthesis. Ultimately, inactivation of all of the host cell EF-2 molecules causes death of the cell.

Thic, grayish, adherent excudate = Pseudomembrane Diphtheria

BUT LOCAL SYSTEMIC INFECTION EFFECTS (throat) (heart, peripheral nerves) Treatment of Diphtheria

- neutralization of toxin (horse serum antitoxin)

- eradycation of bacteria ( penicillin, erytromycin)

PREVENTION: immunization with toxoid DTaP triple vaccine (+tetanus toxoid & pertussis antigens) Other coryneforms

 Corynebacterium ulcerans can carry diphtheria gene-tox may produce diphtheria infection (transmission can also occur through food vehicles such as milk or other dairy products- zoonosis)

 Corynebacterium urealyticum- important pathogen of urinary tract Corynebacterium amycolatum- opportunistic pathogen capable of causing endocarditis and sepsis

 Corynebacterium jeikeium –opportunistic pathogen of immunocompromised patients

Listeria monocytogenes

Reservoir: environment, Habitat: environment Transmission: food-borne, vertical -

- capable of growth at 4°C - motylity - facultative intracellular bacteria - : pregnant women: miscarriage, premature delivery, serious infection of the newborn (septicemia, meningitidis)

Immunocompromised patients: generalized infections symptoms of listeriosis include fever, muscle aches, sometimes nausea or diarrhea. If infection spreads to the , symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions can occur

Erysipelothrix rhusiopathiae growth: 5–42°C reservoir : animals (zoonosis) In humans - three different diseases: . (focal infection /fingers or hands) . generalized skin infection . sepsis (with endocarditis or without; with or without skin lesions) risk groups: people handling animals and products of origin animals (doctors,veterinary students, etc.)