MMI 301: Lecture 18: Enterobacteriaceae

• Large gram - bacilli
• E. coli, Klebsiella, Proteus, Salmonella, Shigella, and Yersinia

• Ubiquitous in soil, water, GI flora
• 40 genera
• >150 species/subspecies
• <20 species responsible for 95% of infections

positive

No spores formed

Facultative anaerobes

Some encapsulated

resistant

Used to differentiate lactose fermenting from non-lactose fermenting

• Serotypical "fingerprint" based on antigenic features: O-antigen-polysaccharide (LPS), H-antigen flagella, K antigen capsules
• Test by looking for agglutination in response to specific antisera

• UTI: O1, O4, O6, O75
• Hemorrhagic Colitis/Hemolytic Uremic Syndrome: O157:H7
• Meningitis: K1

Strains of O:K:H antigens that are associated ubiquitously with certain pathogens imply they evolved away from other lineages to exchange with. These completely similar strains are clones.

• •Endotoxin(LPS)- endotoxin leading to shock
• •Capsule -poor immunogens & antiphagocytic
• •Antigenic phase variation- K & H antigens
• •Type III secretion- syringe-like injectors
• •Sequestration of iron- different siderophores
• •Serum resistance – OmpA binds C4BP
• •Exotoxins - variety of enzymatic and lytic toxins

• •Diarrhea: frequent, liquid stools (stools that assume the shape of their container).
• •Dysentery: a disease marked initially by frequent watery stools but followed by scant stool production characterized by excretion of mucus and blood.  There is usually abdominal pain, fever, and tenesmus.
• •Enteritis:  inflammation of the intestine.
• •Enteric fever:  an acute illness presenting as fever, headache, abdominal pain, and occasional skin rash.  There is bacteremia.
• •Food poisoning:  the ingestion of a food containing a preformed toxin.  No growth of the
• bacteria required in the host. 
• •Emesis:  vomiting

• Number 2 killer of children after pneumonia
• Bangladesh: 7 srs infections a year for first two years
• US: average 2 cases a year

• Lactose Fermenter
• Oxidase +
• Motile (Flagella)
• Most common facultative aerobic
• Gram neg rod in GI tract

• •Enterotoxigenic (ETEC)
• •Enteroinvasive (EIEC)
• •Enteropathogenic (EPEC)
• •Enterohemorrhagic (EHEC)
• •Enteroaggregative (EAEC)
• •Diffuse aggregative E. coli (DAEC)

• Septic Shock/UTI (UPEC)
• Neonatal meningitis

• Most usually from initial infection of GIT/UT
• High mortality in immunocomp/ primary abdominal/CNS infection
• E. coli is leading cause of endotoxic shock/death

• Too much inflammation from gram - septicemia (LPSs)
• IL-1/6 produced by macrophages/lymphocytes/endothelial/keratinocytes and causes fever by release of prostaglandins in hypothalamus, contributes to hypotension/anorexia/increased PMNs/Increased transferrin

• •E. coli (2nd) and group B streptococci (1st) cause majority of CNS infections in infants younger than 1 month
• • 75% of E. coli possess K1 capsular antigen
• •Commonly found in GI tract of mother and child

• Contamination of urethra from colon
• Ascends urethra to bladder, can infect kidneys and prostrate
• Type I pili under phase shift
• Causes 70-90% of uncomplicated UTI
• Cystitis Symptoms: dysuria, frequent and urgent need to urinate

• Colonizes small intestines
• Infant diarrhea in undeveloped countries
• Symptoms: Watery diarrhea, vomiting, nonbloody stools, fever
• Has Bundle-forming pili (BFP)
• Characterisitic attachment/effacement (A/E) lesions
• Recently recognized "atypical" EPEC are frequent cause of diarrhea

• Colonizes human large intestines Cattle can carry, pass on through feces
• Few as 10 bacteria can cause disease
• Between diarrhea-hemorrhagic colitis
•     -HC: diarrhea to bloody stool
• A/E legions and Shiga toxin, EHEC toxin encoded by prophage

• Happens in small number of EHEC infections
• Presents with: Acute renal failure, Thrombocytopenia, Microangiopathic hemolytic anemia
• Severe sequelae in 30%
• Death in 3-5%

• Colonizes small intestine, illeum
• -Infant diarrhea/traveler's diarrhea
• -Symptoms: watery diarrhea, vomiting, cramps, nausea, low-grade fever, no inflammation of intestinal mucosa
• -Heat-labile toxins (LT-I, LT-II) and heat-stabile toxins (STa, STb)
• LT-1 and STa associated with human disease-mediate hyper secretion of fluids/electrolytes

• Mediates attachment to GI epithelial with no invasion, leads to net fluid output by cells
• LT-1 Toxin similar to cholera toxin (AB5 toxin)
• STa is peptide that binds guanylate cyclase increasing cGMP levels and fluid loss

• Colonizes large intestine
• Disease in developing country children
• Symptoms: fever, cramping, watery diarrhea, progress to dysentery
• Closely related to Shigella
• Bacteria invade and destroy colonic epthelial

• Colonizes small intestine
• Infant diarrhea/traveler's diarrhea
• Symptoms: persistent watery diarrhea, vomiting, dehydration, low-grade fever
• Autoaggregate in 'stacked brick' formation
• Shorten microvilli and stimulate mucus production

• Watery diarrhea in children
• Vomiting common
• Stimulates elongation of microvilli into finger-like projections which wrap around bacteria (embedding)

• Does not ferment lactose
• Non-motile

dysenteriae, flexneri, boydii, sonnei

Invasion plasmid antigen (Ipa), Shiga toxin (S. dysenteriae only)

Kiyoshi Shiga (1898)

Simon Flexner (1900)

• No animal reservoirs, all human
• High communicable (100 bacteria will cause disease)
• Fecal vector

• 1. Induces endocytosis in M cells
• 2. Transport to macrophage in lamina propria
• 3. Escapes macrophages and uses invasins to enter enterocyte
• 4. Escape phagosomes by lysis
• 5. Forms actin filaments propelling bacteria through cytoplasm
• 6. Invades adjacent cells
• REMEMBER FROM EXAM 2

• S. sonnei in developed countries
• S. flexneri in undeveloped countries

• Estimated 150 million cases
• 70% of cases in children
• Fecal-->oral
• Infects colon
• Symptoms: abdominal cramps, diarrhea, fever, bloody stools, can progress to HUS
• Symptoms 1-3 days after ingestion
• Can have asymptomatic carriers
• Dysentery: severe shigellosis caused by S. dysenteriae

• •Diffuse erythema and swelling of mucosa
• •Focal hemorrhages and purulent exudate
• •PMN infiltration into intestinal epithelium
• •Formation of intestinal crypt abscesses
• •Excessive inflammatory response
• •Delayed apoptosis and cytokine response by 
• mono-nuclear phagocytes (macrophages)

Yes

Lactose +

• Community-acquired primary lobar pneumonia
• Necrotic destruction of aveolar spaces, cavity formation, blood tinged sputem
• Alcoholics and people with compromised pulmonary function most at risk

• Several common species
• Chronic UTI
• Associated with kidney stones
•    -Produces urease, converts urine to ammonia/CO2
•    -Leads to alkalinization of urine and precipitation of dissolved salts.

• Highly motile, will not form colonies on plates, rather swarm
• Swarming is diagnostic hallmark

• Most of the genera are considered members of normal flora of animals
•     -Not Salmonella, Shigella and Yersinia
•      -Shigella only in humans/apes
•      -Salmonella typhi only in humans
•      -Klebsiella and Proteus have enviromental reservoirs

• Negative/Cannot ferment: Shigella, Salmonella, Proteus, Yersinia
• Positive/Can ferment: Escherichia, Klebsiella, Enterobacter