Enteric Bacteria

General Info
-any bacteria that inhabit the GI tract as commensal or pathogen
-few found in stomach or small intestine (except ileum)
-larger intestine has >90% anaerobe, the remainder are facultative G- rods
-1st step to identify G- rod is the ability to ferment glucose and oxidase test
Enterobacteriaceae
-facultative G- rods that ferment glucose, oxidase negative, and non-spore forming
-isolation on MacConkey agar – selection agars contain lactose as sole sugar source
-Salmonella, Shigella, and Yersinia do not ferment lactose
-identification of isolate based on biochemical tests (citrate and indole tests)
-serotypes based on agglutination to three main surface Ag
-O somatic Ag is the terminal moiety of LPS – heat stable
-H Ag are flagellar – heat labile
-Capsular Ag are acid sugars – may block agglutination with anti-O serum
-K Ag of E. coli, Vi Ag of S. typhi, and serotype Ag of K. pneumoniae
Shigella
-non motile, non-fermenter of lactose, H2S negative
-not considered part of the normal flora – close relative of E. coli
-Group A (S. dysenteriae) produce severe disease – produce Shiga toxin
-Group B (S. flexneri) and Group D (S. sonnei) are common in the US
-clinical manifestations range from asymptomatic to bacillary dysentary
-cramps, tenesmus, and fever with low volume, bloody, mucoid stool
-high number of fecal leukocytes
-HUS is major complication of shiga toxin
-Reiter’s syndrome may develop post infection – polyarthritis and uveitis
-infectious dose is very low due to acid resistant travel thru stomach
-transient growth in small intestine and colonization of the colon
-invades colonic epithelial cells thru M cells – limited to mucosal surface
-bacteremia is not common
-induces apoptotic death of macrophages in the lamina propria
-acute inflammation and mucosal destruction create ulcers and abcesses
-cell to cell spread via release from dead cells or direct passage via vacuole
-utilizes host cell actin as a means of motility – actin tail formation
-virulence factors are found on a large plasmid – chromosomal genes are also needed
-coordinated regulation is temperature dependent – invasive at 37° C
-shiga toxin is both cytotoxic and enterotoxic – may act as a neurotoxin as well
-RNA N-glycosidase that inactivates ribosomes by adenine removal
-transmission is fecal/oral – human specific and highly contagious (ID = 200)
-children are at highest risk – day care center, crowding, and poor sanitation
-stool cultures used in acute stage with MacConkey agar
-TSI is alkaline over acid with no gas
-usually self-limiting disease – fluid replacement, do not impair GI motility
-TMP/SMX used in severely ill – no effective vaccine
-hand washing is best method for prevention
Salmonella
-identical to Shigella except they are motile and do produce H2S
-classified based on O, H, and K Ag
-typhoidal salmonella primarily infects humans -- transmission is fecal (human)/oral
-non typhoidal salmonellae infects many animals – transmission is fecal (animal)/oral
-salmonella cause three main types of diseases
-enterocolitis – diarrhea from S. enteritidis or S. typhimurium
-high incident in US – disease of the industrial world – no vaccine
-nausea, vomiting, cramps, and diarrhea (may be bloody with few leukocytes)
-stomach acid kills many Salmonella – colonization of small intestine
-production of enterotoxin and invasion of mucosa in ileum and colon
-large virulence plasmid is present
-treatment is fluid replacement – no antibiotics are usually given
-enteric fever – typhoid fever from S. typhi and S. paratyphi A,B
-major cause of morbidity and mortality in developing countries (esp. kids)
-10 to 14 day incubation followed by constitutional symptoms
-early constipation followed by bloody diarrhea – abdominal rose spots
-diagnosis by stool culture – 80% positive 1st week, variable beyond 1st week
-adhere to and kill M cells – penetrate lymph follicles
-invade macrophages and disseminate in blood
-spread to many organs – especially liver and spleen
-complications include toxemia (myocarditis), GI lesions, and carrier state
-virulence of S. typhi based on Vi capsule Ag – inhibits complement killing
-lacks virulence plasmid of entercolitis causing Salmonella
-Ab against Vi are protective – possible vaccine
-chloramphenicol or ampicillin are used – also TMP/SMX
-sustained bacteremia – caused by S. typhimurium and S. cholorae-suis
-often 2° infection in debilitated patients (cancer, etc...)
-may lead to focal lesions in lung, bones, and meninges
-increased susceptibility to endocarditis and osteomyelitis
-chronic infections occur in patients with Schistosoma mansoni
-chloramphenical or ampicillin are used – also TMP/SMX
-humans are the sole reservoir for S. typhi – asymptomatic food handlers are problematic
-may persist in the gall bladder
-non typhoidal salmonella exists in almost all animal species
-prevention thru hand washing and improving sanitation
Yersinia
-non lactose fermenters with optimal growth at 22-25° C – not motile at 37°C
-Y. pestis is the causitive agent in the Plague
-Y. enterolitica and Y. psuedotuberculosis are 1° animal pathogens
-fecal/oral route of transmission
-enterocolitis presents with fever, diarrhea, cramps, bloody stool with leukocytes
-Reiter’s syndrome is possible – septicemia is rare
-mesenteric lymphadenitis mimics appendicitis
-similar to S. typhimurium – replicate within macrophages – produce heat stable toxin
-Y. pseudotuberculosis may penetrate ileal mucosa to enter lymph nodes
-virulence factors include chromosomal and plamid genes
-invasins are on chromosome, and outer membrane proteins are on plasmid
-Y. enterocolitica also produces the heat stable toxin
-dramatic increase in incidence over last 10 years
-serotypes O3, O8, and O9 of Y. entercolitica and O1 of Y. pseudotuberculosis
-O3 and O9 in Europe, O3 in Canada, and O8 in the US
-no treatment necessary unless septicemia develops – aminoglycosides or tetracycline
-hand washing and sanitation for prevention – no vaccine
Escherichia coli
-lactose fermenter that is both a normal commensal and frank pathogen – may cause bacteremia
-intestinal diseases caused by diarrheagenic E. coli
-evolved from commensals thru acquisition of virulence factors
-each class is associated with an O:H serotype – not related to virulence
Enterotoxigenic E. coli (ETEC)
-causes acute secretory diarrhea – watery w/o blood or leukocytes
-classic travelers diarrhea
-adhere to small bowel with specific colonization fimbriae (plasmid encoded)
-produce heat labile (LT) or heat stable (ST) toxin (plasmid encoded)
-LT is similar to cholera A/B type toxin -- ↑ intracellular cAMP
-ADP ribosylates GS protien of cyclase complex
-ST increases intracellular cGMP via guanylate cyclase
-no bacterial invasion occurs
-children in endemic areas are at high risk (developing countries)
-650 million cases of pediatric diarrhea per year
-prevention by improved sanitation – no vaccine available
-Ig against CF may be a means of passive protection
Enteroinvasive E. coli (EIEC) – often confused with Shigella
-bacillary dysentary identical to shigellosis – low volume with blood and neutrophils
-carry same invasion plasmid of Shigella
-human specific disease – spread is from infected person
-does not ferment lactose – all other E. coli do ferment lactose
 Enteropathogenic E. coli (EPEC)
-acute and chronic diarrhea in infants – watery w/o blood, may have leukocytes
-produce attaching and effacing (A/E) lesions – effacement of brush border
-virulence factors include:
-bundle forming pilus (BFP) – plasmid encoded mediator of adherence
-not required for A/E lesions
-intimin (required for A/E lesions) and other secreted proteins
-encoded on chromosome pathogenicity island
-highest incident in children < 2 years old – rarely found in adults
-breast feeding is protective – no vaccine available
Enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli (STEC)
-cause a spectrum of disease – mild diarrhea, hemorrhagic colitis (HC), and HUS
-copious bloody diarrhea with cramps in HC – no fever and non-invasive
-O157:H7 is major EHEC serotype in US – low infectious dose
-produces A/E lesions identical to EPEC
-carry chromosomal pathogenicity island coding intimin
-produce bacteriophage-encoded Shiga toxin – associated with HUS
-STEC also produces the bacteriophage-encoded Shiga toxin
-lacks the pathogenicity island – no A/E lesions
-both reside as commensal in cows – contaminate food/water or undercooked meat
-no vaccine, but Ab against Shiga toxin may provide passive protection for HUS
-screen for O157:H7 on SMAC agar – does not ferment sorbitol
-DNA probes and serotyping are necessary to identify various diarrheagenic E. coli
Vibrionaceae
-comma shaped G- rods, glucose fermenters, oxidase positive with polar flagella
-abundant in marine and surface waters
Vibrio cholerae – humans are only known host
-grows well at 37°C with hi salt concentration and hi pH
-classified on the basis of the O Ag
-O1 consists of Classical and El Tor
-O139 genetically resembles El Tor – caused epidemics in India
-codes for an additional polysaccharide capsule
-acute diarrhea caused by enterotoxin
-incubation period (1-4 days) followed by sudden onset of watery diarrhea – no fever
-rice water stools (mucus, cells, and vibrios) with rapid fluid loss
-cholera gravis may reach 1 L per hour of fluid loss
-survive acid in stomach and attach to brush border to multiply
-Tcp pili required for colonization – no invasion of epithelial cells occurs
-cholera toxin encoded on bacteriophage that uses Tcp pili as a receptor
-heat labile toxin with similar action to E. coli LT
-B subunit binds GM1 ganglioside on epithelial cells
-A subunit activates adenylate cyclase via ADP-ribosylation
-increased secretion of Cl- from crypt cells
-decreased NaCl absorption from villus cells
-transmission thru contaminated water or undercooked seafood
-bicarb buffer or fish and rice meals lowers ID50
 Vibrio parahemolyticus
-causes acute, watery diarrhea after short incubation period (hours)
-most virulent strains produce Kanagawa toxin – hemolysin
-cytotoxic and cardiotoxic activities
-associated with eating undercooked seafood – common in Japan and gulf states
Vibrio vulnificus
-causes wound infections and gastroenteritis leading to fatal septicemia
-transmission thru sea water contact (wounds) or eating raw oysters (septicemia)
-liver disease and hemochromatosis are risk factors
Campylobacter jejuni
-comma shaped, G- rod, oxidase positive and microaerophilic
-found in normal flora of many animals
-causes enteritis with fever, cramps, and diarrhea – watery or bloody with neutrophils
-acute colitis and bacteremia may also occur
-Reiter’s syndrome is possible following infection
-40% of Guillain Barre patients had Campylobacter infection prior to symptoms
-adhere to small intestine with invasion of tissue and inflammation – colon may be a target
-transmission by contaminated food/water or contact with infected animals (dogs)
-may be more frequent than Salmonella or Shigells
-isolation from blood or stool on selective media containing antibiotics
-grown at 42°C in reduced O2 (5%)
-treat with fluid replacement and erythromycin
Helicobacter pylori
-motile, spiral shaped microaerophilic and urease positive
-cause of chronic gastritis and peptic ulcers
-implied risk for gastric carcinoma and marginal zone lymphoma
-transmission is by oral ingestion – found in feces, dental plaques, and gastric contents
-penetrates gastric mucus and colonizes epithelium
-toxins and urease damage gastric epithelium causing an inflammatory response
-vacuolation of epithelium leads to ulceration
-virulence factors include:
-urease which converts urea to ammonia and CO2 – helps survival in low pH
-flagella may allow penetration of gastric mucus
-VacA cytotoxin may damage cells
-CagA protein is located within a pathogenicity island – more likely to produce ulcers
-present in vast majority of people worldwide
-mixed infections are uncommon within same host
-husbands and wives rarely exchange strains – children will have one or the other
-diagnosis by gastric biopsy and culture similar to C. jejuni except temp. at 37°C
-may detect urease in biopsy or breath test to detect radiolabeled CO2
-serologic tests of plasma and salivary IgG or IgA – cannot tell if infection is active
-treatment with bismuth subsalicylate and amoxicillin (tetracycline) and metronidazole
-two week course – vaccines are in developement
Pseudomonadaceae
-aerobic G- rods that oxidize but don’t ferment glucose, oxidase postive with polar flagella
-ubiquitous in soil, water, plants, and animals
Pseudomonas aeruginosa
-produce grape-like odor and may be flourescent green (pyoverdin)
-grows between 37° and 42° C
-present in moist environments and can form biofilms
-resistant to disinfectants and preservatives
-opportunistic pathogen causing nosocomial infections
-impaired immune system or previous injury increase risk
-may cause UTI, bacteremia, necrotizing pneumonia, endocarditis, and meningitis
-ear and lung infections with sepsis in compromised patients
-also causes swimmer’s ear
-cystic fibrosis patients may develop chronic infections
-produce a mucoid strain with an alginate capsule
-often co-infected with Staph. Aureus
-virulence factors include:
-pili that mediate adherence to host cells
-exotoxin A – identical to ADP-ribosylation of EF-2 by diptheria toxin
-prevents protein chain elongation
-exotoxin S also ADP-ribosylates proteins – unknown target site
-proteases cause tissue destruction and allow access to deep within tissues
-elastase, collagenase, lecithinase, and alkaline protease
-hemolysin (phospholipase C)
-drug resistance is a problem – evolves resistance rapidly
-use penicillin and aminoglycoside or ceftazidime
Extraintestinal Enteric Bacterial Infections
-ascending UTI (most common route) – may result in cystitis or pyelonephritis
-hematogenous UTI – infection via bloodstream
-Salmonella, Staph. Aureus, and Candida
-uncomplicated UTI – caused mostly by E. coli
-most common in females (during first year, then during sexual activity)
-diagnosed with clean catch of midstream urine – mixed species = contamination
-positive with 105 bacteria per mL – treat with TMP/SMX
-complicated UTI – occur in catheterized or immunosuppressed patients
-Proteus mirabilis is most common infectious agent – wider spectrum of causative agents
-swarming motility on agar with predilection for upper urinary tract
-associated with kidney stone formation via urease action increasing urine pH
-more common among older men – prostrate hypertrophy
-mixed species common in urine sample – positive at 102 to 104 bacteria per mL
-Uropathogenic E. coli (UPEC) carry pathogenicity island encoding P fimbriae and hemolysin
-neonatal meningitis from E. coli expressing K1 antigen – greatest risk within 4 weeks of life
-1° lobar pneumonia caused by Klebsiella pneumonia – greater risk with alcoholism
-urease positive lactose fermenter, non-motile with capsule (anti-phagocytic)
-Septicemia and endocarditis from Enterobacter (encapsulated) and Serratia marcescens
-both contaminate parenteral fluids – Serratia produces a red pigment