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Bacteriology lecture 18,19 Enteric bacterial infections


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Define enteric bacteria
All bacteria that inhabit the GI tract as commensals or as pathogens
What is the typical bacterial flora in the large intestine
Abundant: >90% anaerobes, 10% facultative Gram-negative rods (E. coli, staphylococci, enterococci and yeasts)
What are the four general clinical syndromes of enteric intestinal infections
Watery diarrhea; Dysentery; Hemorrhagic colitis; Enteric fever
What are the characteristics of watery diarrhea
Large volume; no leukocytes; nausea, vomiting, fever; Due to the action of bacterial enterotoxins
What are the characteristics of dysentery
Small volume stools containing blood and pus (inflammatory diarrhea). Fever, abdominal pain, cramps and tenesmus. Due to direct bacterial invasion or the production of cytotoxins
What are the characteristics of hemorrhagic colitis
Bloody diarrhea with or without inflammation. Linked to Hemolytic uremic syndrome
What are the characteristics of enteric fever
Systemic infection originating in the gastrointestinal tract. Penetration of the small bowel with spread to the biliary tract, liver, mesentery and reticuloendothelial system. Typhoid fever is a classic example
What are the main diseases caused by enteric gram-negative bacilli
Intestinal infections; Gastritis and peptic ulcer disease; Extraintestinal infections
The vast majority of intestinal diseases caused by enteric bacteria are caused by which type of bacteria
Frank pathogens
What are the six main families of enteric bacteria covered in class
Enterobacteriaceae; Campylobacteriaceae; Vibrionaceae; Helicobacter species; Pseudomonadaceae; Acinetobacter species
What are the laboratory characteristics of Enterobacteriaceae
Bacilli; Glucose fermenters; Oxidase negative; peritrichous flagella
What are the laboratory characteristics of Campylobacteriaceae
Tiny gull-shaped rods; microaerophilic; oxidase+
What are the laboratory characteristics of Vibrionaceae
Comma-shaped rods; Glucose fermenters; Oxidase+
What are the laboratory characteristics of Helicobacter species
Tiny, curved bacilli; Microaerophilic; urease+
What are the laboratory characteristics of Pseudomonadaceae
Bacilli; Nonfermenters; oxidase+
What are the laboratory characteristics of Acinetobacter species
Bacilli; nonfermenters; oxidase-
What is one of the first steps towards identifying an enteric gram-negative rod
Testing for the capacity of an isolate to ferment glucose
What is the habitat of the enterobacteriaceae
The lower intestinal tract of humans and other animals
Which enterobacteriaceae do not ferment lactose
Shigella sp, Salmonella sp, Yersinia sp.
What three surface antigens are used to identify subsets of a species of enterobacteriaceae
O somatic (terminal moiety of the LPS molecule); H (flagellar antigen, heat labile); Capsular (acid polysaccharides, poorly immunogenic)
What are the general characteristics of the Shigella spp
Gram negative, non motile, non-fermenter of lactose, H2S negative. Not considered normal human flora
What is the group A Shigella serotype
S. Dysenteria. Rare in the US, produces most severe disease (shiga toxin)
What is the group B Shigella serotype
Shigella flexneri. Most common in developing countries and among Native Americans
What is the group C Shigella serotype
S. boydii (rare)
What is the group D Shigella serotype
S. sonnei. Most common in the US and developed countries
What are the main diseases of Shigella spp
Shigellosis; bacillary or colonic dysentery
Abdominal cramps, tenesmus and fever can occur in symptomatic infections of what microbe
Shigella spp, which can cause Shigellosis or bacillary dysentery
What are some common complications in Shigella diseases
Convulsions in children; Hemolytic uremic syndrome; Reiter's syndrome
What is Reiter's syndrome
Post infection complication of Shigella infection consisting of aseptic polyarthritis, uveitis, and painful urination. Occurs in patients with the HLA-B27 histocompatibility antigen
What are the specific steps of Shigella pathogenesis
1. Transit through the stomach (infectious dose is very low)
2. Transient multiplication in the small intestine (enterotoxin production that produces watery diarrhea)
3. Colonization of the colon
4. Invasion of colonic epithelial cells (Pass through M cells and then invade epithelial cells from the basolateral surface)
5. Cause death of macrophages in the lamina propria by inducing apoptosis
6. Escape from the vacuole followed by cytoplasmic multiplication
7. Cell to cell spread
How does cell to cell spread occur in Shigella infections
The bacterium induces an actin tail formation using host cell actin. It then releases itself from dead cells into the lamina propria, or directly passes between cells without exposure to the extracellular environment
Intense, acute inflammation and destruction of colonic mucosa is indicative of what
Invasion of colonic cells by shigellae. Death of mucosal cells creates ulcers and abscesses. Bloodstream dissemination is rare
What do Shigellae carry that is responsible for numerous aspects of shigella pathogenesis, including invasion of host cells and cell to cell spread
A large virulence plasmid
What toxin does Shigella dysenteriae type 1 produce
Shiga toxin
What are some characteristics of Shiga toxin
Cytotoxic and enterotoxic activities; inhibits protein synthesis in eukaryotic cells (28S of 60S); chromosomally encoded or transferred by bacteriophage
How is Shigella transmitted
Fecal/oral route, low dose. Shigellae are human specific.
What is the epidemiology of Shigellae
~18,000 cases of shigellosis are reported in the US annually; children 1-4 are most susceptible; crowding and poor sanitary conditions; enormous impact on military campaigns
How is Shigella diagnosed in the acute stage
Bacteria is present in large numbers in stool. Look for slow or nonfermenters of lactose
How is Shigella treated
Self limiting--do not impair intestinal motility. Trimethoprim/sulfamethoxazole for severly ill. Improve sanitary conditions. No vaccine available
What are the general characteristics of Salmonella sp
Facultative gram-negative rods, non-lactose fermenters, produce H2S, mostly motile
What are the two Salmonella species
S. enterica and S. bongori (bongori not very pathogenic)
What antigens are Salmonella serotypes based on
What is the agent of typhoid fever
Salmonella enterica Typhi
How is typhoidal salmonella transmitted
It primarily infects humans, so its transmission is via ingestion of food or water contaminated with infected human fecal material
What are the clinical manifestations of enterocolitis
Onset 6-48 hours after ingestion; nausea, vomiting, fever, ab pain, diarrhea; Self limiting
What is the pathogenesis of enterocolitis
Transit through stomach (many die) and colonization of small intestine; Multiplication and elaboration of an enterotoxin; Invasion of epithelium in terminal ileum and colon; recruitment of PMNs via IL-8; small numbers invade the submucosa
What are the clinical manifestations of enteric fever (typhoid or paratyphoid fever)
Incubation period 10-14 days; fever, anorexia; early constipation, late bloodly diarrhea; Rose spots on abdomen and chest
How is laboratory diagnosis of typhoid fever made
During the first week of Salmonella typhi infection, 80% of blood cultures are positive; 30-70% of stool cultures are positive in 2-4 weeks
What is the pathogenesis of typhoid fever
Bacteria adhere to and kill M cells, then penetrate intestinal lymph follicles; Multiply in macrophage vacuoles then disseminate through bloodstream to liver and spleen
What are the complications of typhoid fever
Secondary to toxemia (myocarditis, hepatic and bone marrow damage)
Secondary to GI lesions
Secondary to persistence
What produces a N-acetyl galactosaminuronic acid surface polymer called the Vi capsule (antigen)
Salmonella typhi. The antigen inhibits complement mediated killing
What bacteria frequently cause sustained bacteremia with or without focal lesion
Salmonella typhimurium and Salmonella cholerae-suis
What are the clinical manifestations of bacteremia
Fever, chills, weight loss; seen in patients with cancer
What is the pathogenesis of bacteremia
Can lead to focal lesions in lungs, bones, and meninges; subject to osteomyelitis, endocarditis. AIDS patients have higher risk.
Chronic, systemic infections of bacteremia may be caused by what
Schistosoma mansoni due to direct infection of the parasite by the salmonellae
Who are the reservoirs for Salmonella typhi
Humans are the sole reservoir. Can persist in the gall bladder. Infectious dose for Salmonella typhi is lower than for the enterocolitis-causing salmonellae
Who are the principal reservoirs for nontyphoidal salmonella
What is the incidence of typhoid fever
It was the most common type of salmonelloses in the US until the mid 1900s. Enterocolitis is now the most common form
What is the incidence of enteric fever
Salmonella typhi is a major cause of illness in developing countries; school aged children most at risk.
What is the incidence of salmonella enterocolitis
High incidence in the US. It is a disease of the industrialized world, due to large-scale food processing.
What is the treatment for enterocolitis
Fluid and electrolyte replacement; antibiotics generally not needed
What is the treament for enteric fever and bacteremia
Chloramphenicol or ampicillin. Can also use Trimethoprim/sulfamethoxazole or third generation Cephalosporins
What vacines are available for Salmonella infections
None for enterocolitis. Enteric fever include killed whole cell, live strain, and purified Vi antigen
What are the general characteristics of Yersinia sp
Facultative gram negative rods; non-lactose fermenters; optimal growth at 22-25 C. Not motile at 37C
What are the medically important Yersinia species for humans
Y. enterocolitica, Y pseudotuberculosis, Y pestis
How are Yersinia enterocolitica and Y pseudotuberculosis transmitted
They are primarily animal pathogens. Transmission occurs via ingestion of contaminated food
What are some diseases caused by Yersinia sp
Enterocolitis; Mesenteric lymphadenitis (entero and pseudo); Extraintestinal infections; Reiter's syndrome
What is the pathogenesis of Y enterocolitica and pseudotuberculosis
Similar to Salmonella typhimurium, enteriditis. Enters Peyers patches and replicates. Lymph node involvement, and can replicate in macrophages. Heat stabile toxin
What are the virulence factors of Yersinia sp
Chromosomaly-encoded invasins; Plasmid-encoded outer membrane proteins; heat stable enterotoxin (enterolitica)
What is the epidemiology of Yersinia
Highest rates in Scandinavia and Europe; Only certain serotypes are associated with disease; may need to alert lab to look for it.
What treatment is needed for septicemia caused by Yersinia sp.
Aminoglycosides, tetracyclines
What are the general characteristics of E coli
Facultatively gram negative, lactose fermenters. Cause intestinal and extraintestinal disease.
What are the classes of diarrheagenic E coli
Enterotoxic, Enteroinvasive, enteropathogenic, shiga toxin producing, enterohemorrhagic, enteroaggregative
How did diarrheagenic E coli probably evolve
From commensals via acquisition of virulence factors on bacteriophages, plasmids, and pathogenicity islands
What disease is associated with enterotoxic E coli
Acute secretory diarrhea. Copious, watery w/o blood or leukocytes. #1 cause of traveler's diarrhea
What is the mechanism of pathogenesis for enterotoxigenic E coli
Colonization Fimbriae provide attachement, Heat labile and Heat stable toxins are produced. No bacterial invasion occurs
How do Heat labile and Heat stable work
Activate adenylate cyclase and guanylate cyclase respectively
What is the epidemiology of enterotoxigenic E coli
Children in endemic areas, military personnel in endemic areas. Sanitation must be improved; milk with immunoglobulins can be produced. No vaccine
What disease is caused by enteroinvasive E coli
Bacillary dysentery identical to shigellosis. Stools are of scant volume and contain blood and neutrophils
What is the mechanism of pathogenesis of enteroinvasive E coli
They carry a large invasion plasmid of Shigella. Invade cells, multiply in cytoplasm, cell to cell spread
What is the epidemiology of enteroinvasive E coli
Common cause of diarrhea in children in developing countries. Human specific and transmitted from infected persons
What disease is caused by enteropathogenic E coli
Acute and chronic diarrhea in infants. Diarrhea is watery and without blood. May have moderate number of leukocytes
What is the mechanism of pathogenesis in enteropathogenic E coli
Attaching and effacing lesions on intestinal cells that efface the brush border.
What are the virulence factors in enteropathogenic E coli
Bundle forming pilus (mediates intestinal adherence); Intimin (adhesion necessary for formation of attaching and effacing (A/E) lesions)
What is the epidemiology of enteropathogenic E coli
Highest incidence in children <2 years old. Endemic in developing countries. Rarely infects adults. Breast feeding is protective
What diseases are caused by enterohemorrhagic E coli and Shiga toxin producing E coli
Mild diarrhea, Hemorrhagic colitis, and hemolytic uremic syndrome. Emerging infectious agent. Copious, bloody diarrhea occurs in hemorrhagic colitis with severe abdominal cramps. No fever, non invasive
What are the mechanisms of pathogenesis of enterohemorrhagic E coli
O157:H7 is the major US serotype. EHEC produces attaching and effacing lesions (A/E) identical to EPEC. Major site of pathology is the colon. Also produces a bacteriophage-encoded shiga toxin, likely responsible for HUS
What is the pathogenesis of Shiga toxin producing E coli
Produces a bacteriophage encoded shiga toxin, but lacks a pathogenicity island like EHEC, so it does not produce A/E lesions on intestinal cells
What is the epidemiology of Enterohemorrhagic and Shiga toxin producing E coli
> 110,000 illness in the US per year. Reside in commensals in cows and other animals. O157:H7 has very low infectious dose
What is the treatment for enterohemorrhagic and shiga-toxin producing E coli
Antibiotics may inducing toxin-encoding prophage, which can increase the risk and severity of HUS. Blood transfusion and renal dialysis is often performed for HUS
What is enteroaggresive E coli associated with
Acute and persistent diarrhea in children in developing countries. Has colonization fimbriae and heat stable enterotoxins
What type of E coli does not ferment lactose
Enteroinvasive E coli
What strain of E coli does not ferment sorbitol
What are the general characteristics of Campylobacter jejuni
Gram negative, comma-shaped rod, slow growing, motile, oxidase positive, microaerophilic
What diseases are caused by Campylobacter jejuni
Enteritis, colitis; Reiter's syndrome; Guillain Barre syndrome
What are the characteristics of enteritis and colitis caused by Campylobacter jejuni
Fever, ab pain, diarrhea. Bloody stools containing neutrophils, similar to Shigella. Acute colitis may be seen.
What is the pathogenesis of Campylobacter jejuni
Adherence to upper small intestine; invasion of tissue and inflammation. Colon is eventual target. Lipooligosaccharide (LOS) has structure similar to human gangliosides, leading to autoimmune Guillane Barre
How is Campylobacter jejuni transmitted
Undercooked chicken, other fowl
What is the epidemiology of Campylobacter jejuni
Most frequent cause of bacterial diarrhea in the US. High incidence worldwide, more frequent than Shigella or Salmonella
When do symptoms of Guillain Barre syndrome appear
3 Weeks after diarrhea from Campylobacter jejuni
What is the treatment for Campylobacter jejuni
Fluid and electrolyte replacement. Erythromycin in short duration (resistance is increasing)
What are the general characteristics of Vibrionaceae
Comma-shaped Gram negative rods, glucose fermenters, oxidase positive, polar flagella, abundant in marine and surface waters
What serogroups cause chronic cholera
Serogroups O1 (classical and El Tor) and O139 (Bengal) of Vibrio Cholerae
What causes the acute diarrheal disease of cholera
Enterotoxin. There is no bacterial invasion of host tissue. Can range from asymptomatic to cholera gravis
What are the clinical manifestations of cholera
Incubation 1-4 days, no fever but nausea, vomiting and profuse watery diarrhea with cramps; Rice water stools are characteristic.
What is the pathogenesis of Cholera
Survive acid stomach and multiply in bowel. Fimbriae called Toxin coregulated pili (Tcp). Produce cholera toxin
What does the cholera bacteriophage use as a receptor
The Tcp pili
What does the B subunit of cholera toxin bind to
GM1 ganglioside
What is the major bacterial factor responsible for intestinal fluid secretion
Cholera toxin
How is cholera transmitted
Ingestion of contaminated water or food. High dose is required (people actually volunteered to prove this)
What is the epidemiology of cholera
Seven pandemics since 1817. El Tor is the current pandemic (The name comes from the mountain where Moses received the commandments. Now you know).
Children are at greatest risk; risk to travelers; humans are only known host
How is cholera treated
Fluid and electrolyte replacement. Oral hydration therapy works. Use tetracycline if you must
How is cholera prevented
Improved sanitation, Cooked food, vaccines
What are the characteristics of Vibrio parahemolyticus
Acute watery diarrhea. Short incubation period. Produces Kanagawa toxin. Associated with raw or undercooked seafood

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