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Home , Clostridium, Corynebacterium, Corynebacterium ulcerans, Erysipeloid

Gram-positive and rods

Katedra i Zaklad Mikrobiologii UM Wrocław Important terms

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

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

Important terms - anatoxine

TOXIN TOXOID

Toxicity Toxicity anatoxine = toxoid - bacterial whoseAntigenicity toxicity has been weakenedAntigenicity or suppressed; can be used for safe active immunization

Convertion : - heat Stimule active immunity - chemicals (toxoid vacines) Important terms – active immunization active immunization inactivated/killed- stimulation with a specific antigen to promotenon-virulent antibody or attenuated pathogen formation in the body.Bacterial Protection proteins or against may last several polysaccharides years, in some (Subunit/conjugate) cases for life toxoid Important terms - passive immunization

Passive immunity - providing IgG antibodies to protect against (immediate, but short- lived protection) : a) natural passive immunity - 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 to humans as a result of direct or indirect contactwith population Gram-positive Rods

Corynebacteria Not closely related & No cause similar clinical ( forming bacteria) Erysipelothrix conditions do not produce Family: Bacillaceae

- Cl. tetani : - B. anthracis - Cl. botulinum Genus: - Cl. perfringens Bacillus - B. cereus - B. cereus Clostridium - Cl. difficile - product endoepores - Product endoepores - facultative or obligate aerobes - strict anaerobes - many produce - diversity of anaerobic - Wide variety of extracellular (biodegradation & invasive infection)

Bacillus anthracis

• Protein capsule (poly-D-) • Form spores • Three toxin protein components (plasmid-coded )

Bioterrorism agent !!! individulal proteins important in pathogenesis of antrax

• Protective antigen (PA) mediates cell entry of EF &LF

• Edema factor (EF) severe edema (IL-4;disable immune response )

• Lethal factor (LF) necrosis (TNF-α, IL1-β; kill the cell) A-B toxines 2 A-B toxines, which share the same B component

Lethal toxin Subunit A = rapid cell deth by cleaves critical intracellular signaling module

Protective antigen Subunit B = binds toxin to cells and mediates it internalization)

Edema toxin Subunit A = catalyzes production of cyclic AMP within host cell -> dramatic tissue edema

• zoonosis disease • Is not spread from person to person How is anthrax spread?

Getting spores in a Eating contaminated cut or broken skin meat Breathing in spores

CUTANEOUS INHALATION INTESTINAL ANTHRAX ANTHRAX ANTHRAX Cutaneous Anthrax Symptoms

• Develope 1-12 days • Begins like an insect bite • Becomes a fluid- filled blister • Center turns black and becomes sunken Inhalation Anthrax Symptoms

• Incubation time: 1-5 days • Flu-like symptoms • Fever/ chills • Muscle aches • Malaise • Shortness of breath Flu symptoms vs Anthrax symptoms

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 Intestinal Anthrax Symptoms

• Nusea, loss of appetite • Vomiting • Fever • diarrhea

Anthrax Therapy: – , , quinolones – administered before the onset of lymphatic spread!

Prevention: – possible vaccination for „risk” groups – vaccination of animals (Pasteur 1881) – burning of burial of animals that died of anthrax infections

Intravenus Occular infections Catheter related (necrotic toxine, cereolysine, phospholipase C) GASTROENTERITIS

Emetic form Diarrheal form

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

intoxication infection caused by toxin producing in vivo the bacillus of

• Found worldwide in soil and aquatic sediments • Botulus (Latin) = sausage • 15 min, 100°C – destroying of C.botulinum and its toxin • 121°C, 15 min (moist heat) – spores destruction

CLASSIC BOTULISM

Vegetables, fish contaminated with spores Toxine signs appear within 24h – 48h

Improper Appropriate conditions: Toxin process of - Strictly anaerobic environment absorbtion food - Neutral or alkaline pH Spores germination

Bacill multiplying Food is ingested Excrete toxin into the food Botulism

failure of neurotransmission flaccid paralysis

Botulinum toxin acts at the neuromuscular junction to prevent release of acetylcholine, a neurotransmitter that stimulates muscle contraction Manifestations of food-borne botulism

• Very slight gastrointestinal symptoms • No fever, no sign of sepsis • Normal mental status • Descending flaccid paralysis with bulbar signs „4 Ds” –signs of botulinism

1. Diplopia (double vision) 2. Dysarthria (difficulty forming words) 3. Dysphonia (difficulty intoning words) 4. Dysphagia (difficulty swallowing) BOTULISM

• Rare form of botulism • Wound becomes contamined with the , and toxin is absorbed from that site INFANT BOTULISM „ floppy baby syndrome”

Early signs: - Constipation - Feeding problems - lethargy - Poor muscle tone

Not only C.botulinum….. C. baratti, C.butyricum Botulism

CLASSIC BOTULISM INFANT BOTULISM WOUND BOTULISM (intoxication) (infection caused by -toxin producing in vivo in toxin producing in vivo) the wound; - symptoms similar to those of foodborne infection - incubation period is longer_ Treatment

• Antitoxin – trivalent horse antiserum (A, B, E) • Antibiotics ( infant and wound botulism) • Supportive measures (mechanical ventilation) and bioterrorism

Lethal dose of toxin for a 70-kg human: - 0,09 to 0,15 µg intravenously - 0,70 to 0, 90 µg inhaled - 70 µg orally

By contaminating food (unlikely) By inhalation (presence in aerosols) Medical uses of botulinal toxin

• Dystonia • Strabismus • Hyperhydrosis Other: migraine headaches, achalasia, cerebral palsy 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 botulinum toxin

• Normal inhabitants of the herbivores • Produces a round terminal spore („drumstik”) • Do not invade but remain at the side of infection

Clostridium tetani

• – hemolytic toxin

• – neurotropic A-B toxin A – responsible for toxic effect B – binding subunit Tetanospasmin

- Heat-labile, plasmid encoded – Produced during stationary phase of growth – Released when the cell is lysed – It is destroyed by: - heating (65°C, 5min) - action of acid - proteolytic enzymes

Tetanospasmin

- Being internalized & moves from the peripheral nerve terminals to the central nervous system by retrograde axonal transport – Being released from the postsynaptic dendrites – Localized within vesicles in the presynaptic nerve terminals – Acts by blocking the release of inhibitory neurotransmitters (GABA) – Causing exitatory synaptic activity to be unregulated

Tetanus

Predisposing factor for :

- area of low oxidation-reduction potential (necrosis, large splinter) - coinfection with aerobic - others:unskilled abortion, scarification rituals, female circumcision

Tetanus

- generalized - localized - cephalic - neonatal Tetanus

Incubation period: 4 days- several weeks

• Tingling sensation in the vicinity of the wound • Muscular spasms • „ lockjaw” • Risus sardonicus -„sardonic grin” • opisthotonus Treatment

• Surgical management • Tetanus toxoid – active immunisation • Passive immunisation with antitoxin • Critical care unit Complications of Tetanus

•Laryngospasms •Fractures •Hypertension •Nosocomial infections •Pulmonary embolism •Aspiration pneumonia •Death

• Part of normal flora (vagina, GI) • Ubiquitous in nature • Cl. perfringens strains are grouped A through E type

Pathogenesis

Exogenic infection: Endogenic infection: penetrating wound, after gut rupture, septic contaminated with spores abortion (rare) Clostridium perfringens Remember, sometimes just colonization After: - gut rupture - septic abortion GASTROENTERITIS SOFT TISSUE INFECTIONS

SEPSIS

MYONECROSIS NECROTIZING FOOD ENTERITIS POISONING

FASCIITIS SOFT TISSUE INFECTIONS

CELLULITIS FASCIITIS MYONECROSIS = suppurative myositis = gas

 edema  results from cellulitis erythema  systemic spraed  Accumulation of pus gas formation in tissue  necrosiss of muscle  generally nonpeinful in the muscle planes  no necrosis  painful  no sistemic symptoms  gas formation

LOCALIZED ! SYSTEMIC ! -> shock, renal failure Clostridial cellulitis

• No systemic toxemia • Infected tissue looks similar to due to gas bubbles fermentation Myonecrosis (gas gangrene)

Is marked by: high fever intense pain brownish pus gas bubbles (CO2, H2S, CH4) skin decoloration foul odor Clostridium perfringens soft tissue infections

- Typically polymicrobic:

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

- Incubation period in gas gangrene: 1-7 days

Clostridium perfringens pathogenesis

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

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

Role: Dnases Role:

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

Microscopic examination of necrotic tissue reveals: gram-positive rods in the, 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 (food poisoning)

Cl. perfringens type : A B C D E

All produces α exotoxine

Produces the bigest amount of α TOXINE Clostridium perfringens human infections

SOFT TISSU INFECTIONS

FOOD POISONING Cl. perfringens type A

PRIMARY SEPTICEMIA

NECROTIZING ENTERITIS Cl. perfringens type C

C.Perfringens Food-Borne Disease

-Intoxication - abdominal cramps, watery diarrhea - no vomiting, no fever -occurs 8-18h after eating contaminated food (meet products) - lasts 24-48h 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

Treatment – Surgical debriment – Very high dose penicillin – Supportive therapy (HBOT)

Prevention: Cleaning and watching for signs of infection Clostridium difficile

• AAD (- Associated Diarrheas)

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

• Cephalosporins • Ampicillin • Clindamycin 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 weak cytotoxin

Toxin B potent cytotoxin (distrupts protein synthesis)

Resistant casettes (ermB MLS) Diagnosis AAD Presence of diarrhea associated with antibiotic therapy in the preceding 4-6 weeks & recovery of Cl.difficile organism and/or toxin from the stool

PMC demonstration of pseudomembranes by colanoscopy & recovery of Cl.difficile from stool

Treatment

• Oral administration of or

• Avoid: antidiarrheal agents( prevent colonic stasis)

• Volume resuscitation for dehydrated patients

Natural human Can function as flora of: Coryneforms - skin opportunistic = diphtheroids - upper respiratory tract - urogenital tract - gastrointestinal tract

strict pathogens: .lysogenic diphtheriae - Pleomorphic rods . (zoonosis) - Form clumps that look like Chinese characters - 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

occurs through inhalation of saliva spread through direct contact with skin lesions droplets that contain the bacteria of an infected host

Mortality rate : genreal population: 5%–10% children younger than age 5 years and adults older than age 40 years: up to 20% Diphtheria gene for toxin production occurs on the chromosome of the , but a bacterial repressor protein controls the expression of this gene. The repressor is activated by iron. Toxin is synthesized only by lysogenic bacteria under conditions of iron deficiency. responsible for the disease symptoms

Diphtheria should be considered:

- In unvaccinated patients with - 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, skin) (heart, peripheral nerves) Treatment of Diphtheria

- neutralization of toxin (horse serum antitoxin)

- eradycation of bacteria ( penicillin, erytromycin)

- immunization with toxoid

PREVENTION: immunization with toxoid DTaP triple (+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 and sepsis

–opportunistic pathogen of immunocompromised patients

Erysipelothrix rhusiopathiae

Pleomorphic G+ rod distributed worldwide (animals, environment) uncomon human pathogen (occupational disease in people working with animals) (localized or septicemic) – zoonosis complications: endocarditis, formation, osteomyelitis virulence factors: - hyaluronidase - neuraminidase - capsule like structure

- widespread among animals and in an environment - growth at a broad temperature range (1- 45°C) - facultative intracellular bacteria - naturally resistant to cephalosporins

Listeriosis

Although the number of cases of is small, the high rate of death associated with this infection makes it a significant public health concern

sporadic disease in healthy adults ( influenzae-like illnes with or without gastroenteritis), but is serious disease in patients from risk groups: - pregnant women - newborns - immunocompromised patients - eldery Virulence factors: -internalins - - intracellular survival - ActA protein GIT CNS self-limiting febrile gastroenteritis - meningitis syndrome - meningoencephalitis - rhomboencephalitis

LISTERIOSIS

neonatal infections bacteremia and non-CNS focal infections - early onset: granulomatosis focal bone infection infantisepticam native and prosthetic joints infection - late-onset: - pneumonia osteomyelitis - septicemia liver infection - meningitis splenic abscess others… pregnant women: miscarriage, premature delivery amnionitis, Thank you for attention 