Enterobacteria

Enterobacteriaceae

* Medical Microbiology

Enterobacteriaceae

Diversity of species Ecology Found worldwide in soil, water, vegetation, and microbial flora of animals and humans Some are always associated with disease e.g., Shigella, Salmonella, Yersinia pestis Some are normal flora that can become opportunistic pathogens e.g., E. coli, K. pneumoniae, P. mirabilis
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Microbial Physiology and Structure

Cell morphology Moderate-sized Gram negative rods Non-spore-forming Motile (with peritrichous flagella) or non-motile Physiology All are facultative anaerobes Simple nutritional requirements: All genus Ferment glucose Reduce nitrates to nitrites
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Distinguishing Characteristics

Oxidase: Distinguishes among other fermentative and non-fermentative Gram— bacilliLactose fermentation (red colonies on MacConkey agar)Separate Escherichia, Klebsiella, Enterobacter from other non lactose fermenter Enterobacteria *

Distinguishing Characteristics

Resistance to bile salts Separate Shigella and Salmonella from normal flora in this group Eosin Methylene Blue (EMB) Lactose, eosin, methylene blue; E. coli grow with green metalic sheen
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Virulence Factors
AntigensSomatic “O” LPSMajor cell wall Ag; heat stableSpecific “O” antigens associated with each genus; however, cross reactions are commonSalmonella and CitrobacterEscherichia and Shigella *

Virulence Factors

Capsular KpolysaccharideHeat-labileMay interfere with detection of “O”Removed by boiling organismsCapsular antigen of Salmonella typhi referred to as Vi antigen *

Virulence Factors

Flagella H Heat-labile proteins Can be absent or undergo antigenic variation (present in two phases) Specific H antigens assocated with disease
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Virulence Factors

Pili Attachment to host cells an initial step in bacterial colonization
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Pathogenesis of Escherichia

E. coli present in gastrointestinal tract as normal flora Bacterial sepsis (multiplication in blood) Primary focus-infection of urinary tract or spread from gastrointestinal tract Death can occur in immunocompromised patients and infections resulting from intestinal perforation
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Pathogenesis of Escherichia

Neonatal meningitis E. coli and group B streptococci most common 75% E. coli possess Capsular K1 antigen Colonization of infants with E. coli at delivery is common.
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Urinary tract infections (80% community and most nosocomial) Originate from gastrointestinal tract Important virulence factors Resistance to serum-killing Production of toxins e.g hemolysins Pili-mediated binding Production of slime layer that participates in cell adhesion
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Pathogenesis of Escherichia

Gastroenteritis (countries with poor hygiene) Enterotoxigenic (ETEC) Mediated by heat-labile (like cholera) and heat-stable exotoxins (activates guanylate cyclase and stimulates secretion of fluid) Both are coded from plasmid-borne genes World-wide:both adults and children Incubation 1-2 days; persists 3-4 days Mild symptoms, including cramps, nausea, vomiting, watery diahrrea
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Pathogenesis of Escherichia

Gastroenteritis, continued Enteroinvasive (EIEC) Invade and destroy colonic epithelium Fever and cramps with blood and leukocytes in stool Uncommon; often food-borne Enteropathogenic (EPEC; childhood diarrhea) Organism adheres to enterocyte plasma membrane and causes destruction of microvilli producing watery diarrhea Adhesiveness mediated by plasmid-encoded pili
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Pathogenesis of Escherichia

Gastroenteritis Enteropathogenic Infants< 1 year affected Enterohemorrhagic (EHEC; hemorrhagic colitis) Produces cytotoxin (verotoxin) Severe abdominal pain, bloody diarrhea, little or no fever Warm months of year; affects children < 5 years

Pathogenesis of Escherichia

Gastroenteritis, continued Enteroaggregative (EaggEC; watery diarrhea) Infants < 6 months AIDS patients
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Pathogenesis of Different Toxins

Interestingly, E. coli 0:157H:7 has pedestal and Shiga toxin (char. Shigella)
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Pathogenesis of Salmonella
Source of most infections Ingestion of contaminated water, food Poultry, eggs, and dairy products Salmonella typhi spread by food or water; contaminated by food-handlers Need to ingest large number of organisms By fecal-oral contact in children
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Pathogenesis of Salmonella

Gastroenteritis (most common) Symptoms 6-48 hours after ingestion Nausea, vomiting, non-bloody diarrhea Elevated temperature, abdominal cramps, muscle cramps, headache Symptoms persist for 2 days to a week before abating Antibiotics are normally not employed because carrier state can develop
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Pathogenesis of Salmonella

Gastroenteritis (continued) More acid-sensitive than Shigella Infect patients with decreased stomach acid Large inoculum needed Decreased by 10-100X in the presence of bicarbonate
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Pathogenesis of Salmonella

Septicemia (pediatric and geriatric patients) 10% patients can get: osteomyelitis, endocarditis, or arthritis
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Pathogenesis of Salmonella

Enteric fever (S. typhi, typhoid; S. paratyphi, paratyphoid) Paratyphoid is milder Symptoms after 10-14 day incubation period Gradually increasing remittant fever Headache, muscle aches, malaise, and decreased appetite; gastrointestinal symptoms occur Symptoms persist for a few days
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Mechanism of Diarrhea

Exact mechanism of diarrhea unknown Invasion produces IL8 that leads to local leukocyte attraction Ability to invade and produce inflammation necessary, but not sufficient to produce diarrhea; found by experiments in animals Other signal necessary Some have cholera toxin-like molecule
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Pathogenesis of S. typhi
Typhoid Fever Survive in macrophage; studied in mice Causes typhoid-like illness in mice; diarrhea in humans
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Properties of Shigella

Species Shigella sonnei (industrial countries) Shigella flexneri (underdeveloped countries) Pediatric disease (1-4 years) Associated day-care centers, nursuries, and custodial institutions Spread by fecal-oral route (hands) 200 bacilli can establish disease
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Properties of Shigella

Clinical syndromes (1-3 days after ingestion) Abdominal cramps Diarrhea Fever Bloody stools
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Properties of Shigella

PathogenesisColonize small intestine and multiply during first 12 hoursInitial sign of infection—profuse watery diarrhea without histological evidence of mucosal invasionMediated by enterotoxinInvasion of colonic epithelium results in lower abdominal cramps, difficulty defecating, abundant pus and blood in stoolBacteremia is uncommon *

Antibiotic Therapy of Shigella

Antibiotic treatment is recommended to reduce spread to other contactsFluoroquinolines-adultsUnder 17-damage to cartilage and jointsDetermined by animal studiesFDA does not allow use in childrenNew -lactam cephalosporin in use *

Pathogenesis of Shigella

Survival in stomach Sense acid environment Sigma factor RNA polymerase (formed in stationary phase)
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Pathogenesis of Shigella
Survival in stomach (continued) Controls group of genes concerned with acid resistance; acid resistance increased Invasion-ability less When reach small intestine, invasion ability returns and acid resistance repressed Acid resistance enhanced by anaerobic conditions found in large intestine
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Large Intestine Invasion

Bacterial multiplication occurs inside intestinal epithelial cell Invasion and survival multiple genes both on chromosome and plasmid (large virulence)
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S. dysenteriae Pathogenesis

S. dysenterieae type 1 also possesses: shiga toxin cytotoxin-kills intestinal epithelial and endothelial cells
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S. dysenteriae Pathogenesis

Shiga toxin Irreversibly inactivates mammlian 60 S ribosomal SU; stops protein synthesis Mechanism: Targets sodium absorptive villus cell; produces decrease in Na+ absorption; more fluid accumulates in lumen Affects toxin mucosal epithelial cells yielding bloody diarrhea
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S. dysenteriae Pathogenesis

Interestingly, S. sonnei has same invasion process as other two, but with no dysentery, only watery diarrhea Reason for difference between type 1 and others may be difference in intensity of inflammatory response
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Pathogenesis of Yersinia pestis

Clincal syndromes Bubonic plague (incubation period-7 days after bite from infected flea) High fever and inflammation of lymph nodes in groin or armpit Bacteremia (75% die)
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Pathogenesis of Yersinia pestis
Clincal syndromes Pneumonic plague (incubation 2-3 days) Have fever and malaise Develop pulmonary symptoms within 1 day Untreated >90% die
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Pathogenesis of Yersinia enterocolitica

Associated with Contaminated meat or milk Colder climates during winter months
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Pathogenesis of Yersinia enterocolitica

Gastroenteritis Diarrhea, fever, abdominal pain Lasting for 1-2 weeks Chronic form can persist for months or year Can mimic appendicitis, particularly in children Adults can have septicemia, arthritis, intrabdominal abscess, hepatitis, and osteomyelitis
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Pathogenesis of Klebsiella pneumoniae

Associated pneumonia Frequently associated with Necrotic destruction of alveolar spaces Production of blood-tinged sputum Can also cause wound, soft tissue, and urinary tract infections
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Pathogenesis of  Proteus mirabilis

Urinary tract infections Produce large amounts urease Urea into carbon dioxide and ammonia Changes renal pH Facilitates formation of stones Also toxic for uroepithelium Presence of pili may decrease virulence Better phagocytosis
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Prevention and Control

Difficult, because enterobacteria are normal flora Prevention Plague Effective vaccines Prophylactic use of tetracycline for medical workers in contact with pneumonic plague Vaccines for Salmonella typhi
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Prevention and Control
Treatment Use of antibiotic susceptibility testing E. coli and Proteus normally respond well to antibiotic treatment
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