Download chapter 33 - Lange Textbooks

CHAPTER 33
Enterobacteriaceae
The Enterobacteriaceae are a large and diverse family of Gram-negative rods, members
of which are both free-living and part of the indigenous flora of humans and animals. A
few are adapted strictly to humans. They are by far the most common cause of urinary
tract infections (UTIs), and a limited number of species are also important etiologic
agents of diarrhea. Spread to the bloodstream causes Gram-negative endotoxic shock, a
dreaded and often fatal complication.
GENERAL CHARACTERISTICS
I. BACTERIOLOGY
1. Rods are large
2. Many have surface pili (fimbriae)
3. Antigenic components of the cell wall and surface are: O = LPS; K =
polysaccharide capsule; H = flagellar protein
4. Facultative growth is rapid
5. Biochemical characteristics establish species
6. The genera containing the species most virulent for humans are Escherichia,
Shigella, Salmonella, Klebsiella, and Yersinia
7. Antigenic characters define serotypes within species
A. TOXINS
1. LPS endotoxin common to all Gram-negative bacteria is present in all
2. Some also produce protein exotoxins, which act on host cells by damaging
membranes, inhibiting protein synthesis, or altering metabolic pathways.
3. Cytotoxins kill cells
4. Enterotoxins cause secretion and diarrhea
II. DISEASES CAUSED BY ENTEROBACTERIACEAE
A. EPIDEMIOLOGY
1. Present in nature and the intestinal tract
2. Shigella and Salmonella serotype Typhi are found only in humans
B. PATHOGENESIS
a. Opportunistic Infections
1. Colonization presents opportunity when defense barriers open
2. Urinary tract infection (UTI) follows access and adherence to bladder
mucosa
b. Intestinal Infections
1. Salmonella, Shigella, Yersinia enterocolitica, and certain strains of E. coli
are able to produce disease in the intestinal tract
2. Cell destruction causes dysentery
3. Enterotoxins cause watery diarrhea
4. Enteric fever is a systemic illness
c. Regulation of Virulence
1. Virulence factors respond to environment
2. Contact secretion systems inject virulence factors
3. Virulence genes are organized into gene clusters
4. Expression may be stimulated by environmental cues
5. Pathogenicity islands (PAIs) contain foreign DNA
III. ENTEROBACTERIACEAE: CLINICAL ASPECTS
A. MANIFESTATIONS
1. UTI and acute diarrhea are most common
B. DIAGNOSIS
1. Culture is the primary method of diagnosis
2. MacConkey agar demonstrates lactose fermentation
3. Selective media required for Salmonella and Shigella in stools
4. Gene probes allow direct detection
C. TREATMENT
1. Susceptibility to antimicrobials is highly variable
ESCHERICHIA COLI
I. BACTERIOLOGY
1. Most strains of E. coli ferment lactose rapidly and produce indole
2. Over 150 serotypes use O, H, K antigens
A. PILI
1. Type 1 pili bind mannose
2. P pili bind uroepithelial cells
3. Pili of diarrhea strains bind enterocytes
4. Type 1 has on–off switch
B. TOXINS
1. α-hemolysin is pore-forming cytotoxin
2. CNF disrupts intracellular signaling
a. Shiga toxin (Stx)
1. AB toxin produced by Shigella and E. coli
2. Inhibits protein synthesis by ribosomal modification
b. Labile toxin (LT)
1. AB toxin ADP-ribosylates G protein
2. Adenylate cyclase stimulation similar to cholera
c. Stable toxin (ST)
1. ST stimulates guanylate cyclase
II. E. coli OPPORTUNISTIC INFECTIONS
A. URINARY TRACT INFECTION (UTI)
a. Epidemiology
1. E. coli accounts for more than 90% of the more than 7 million US cases of cystitis
and 250,000 of pyelonephritis
2. Perineal flora is reservoir of common cystitis
b. Pathogenesis
1. Minor trauma admits E. coli to the bladder
2. Uropathic E. coli (UPEC) serotypes cause most UTIs
3. Type 1 pili adhere to periurethral and bladder cells
4. The presence of P pili adds an additional component due to the presence of
their Gal-Gal receptor on uroepithelial cells.
5. P pili prominent in pyelonephritis
B. OTHER OPPORTUNISTIC INFECTIONS
1.
2.
3.
4.
5.
E. coli is one of the most common causes of neonatal meningitis
Infection from vaginal flora much like group B streptococcal disease
K1 capsule identical to meningococcus
Non-UTI infections require some breach of defenses
May follow mechanical damage such as a ruptured intestinal diverticulum,
trauma, or involve a generalized impairment of immune function
III. E. coli INTESTINAL INFECTIONS
A. ENTEROTOXIGENIC E. coli (ETEC)
a. Epidemiology
1. Traveler’s diarrhea affects children of developing countries
2. High dose in uncooked foods required
b. Pathogenesis
1. LT and/or ST cause fluid outpouring in small intestine
2. Colonizing factor (CF pili) is required
c. Immunity
onimmunogenic1. sIgA to LT and CFs may provide some protection
B. ENTEROPATHOGENIC E. Coli (EPEC)
a. Epidemiology
1. Nursery outbreaks and endemic diarrheas occur in developing world
2. In developing countries EPEC account for up to 20% of diarrhea in
bottle-fed infants younger than 1 year of age
b. Pathogenesis
1. EPEC initially attach to small intestine enterocytes using Bfp pili to
form clustered micro-colonies on the enterocyte cell surface
2. Intimin receptor and E. coli secretion proteins Esps are injected
3. Cytoskeleton modification produces attachment and effacing (A/E)
lesion
C. ENTEROHEMORRHAGIC E. coli (EHEC)
a. Epidemiology
1. Consumption of contaminated animal products is the main source
2. EHEC disease has emerged as an important cause of bloody diarrhea in
industrialized nations
3. Bloody diarrhea and hemolytic uremic syndrome (HUS) linked to
O157:H7
4. Low infecting dose facilitates transmission
5. Modern meat processing facilitates widespread outbreaks
6. Unpasteurized beverages are another risk
b. Pathogenesis
1. Produce both Stx and A/E lesions
2. Lesions are in colon
3. Stx causes capillary thrombosis and inflammation
4. Circulating Stx leads to HUS
D. ENTEROINVASIVE E. coli (EIEC)
1. EIEC closely resemble Shigella
2. Documented outbreaks in industrialized nations are usually linked to
contaminated food or water
E. ENTEROAGGREGATIVE E. coli (EAEC)
1. Protracted (>14 days) watery diarrhea occasionally with blood and mucus
2. EAEC strains are defined on the basis of the pattern the bacteria make (stackedbrick) when adhering to cultured mammalian cells
3. Adherence and biofilm cause diarrhea
IV. E. coli INFECTIONS: CLINICAL ASPECTS
A. MANIFESTATIONS
a. Opportunistic Infections
1. Dysuria and frequency are features of UTIs
2. If the infection ascends the ureters to produce pyelonephritis, fever and
flank pain are added and bacteremia may develop
3. No clinical features distinguish these cases from those caused by other
members of the Enterobacteriaceae
b. Intestinal Infections
1. Infections caused by all of the E. coli virulence types usually begin with a
mild watery diarrhea starting 2 to 4 days after ingestion of an infectious
dose
2. ETEC and EPEC diarrhea is watery
3. EHEC diarrhea is bloody
4. HUS begins as oliguria and may progress to renal failure
B. DIAGNOSIS
1.
2.
3.
4.
Like the rest of the Enterobacteriaceae, E. coli is readily isolated in culture
Numbers in urine are high (>105) in quantitative culture
Diarrhea requires immunoassay or gene probe
Sorbitol agar screens for O157:H7
C. TREATMENT
1. Resistance influences antimicrobial selection
2. Most E. coli diarrheas are mild and self-limiting
3. Antimicrobics may help all but EHEC
D. PREVENTION
1. Avoid uncooked foods in regions with poor sanitation
2. Chemoprophylaxis for travelers’ diarrhea works for defined periods
3. Recommendations for the irradiation of meats and the extension of
pasteurization requirements to fruit juices are largely designed to stem the spread
of EHEC.
4. Rare hamburgers carry risk for EHEC
SHIGELLA
I. BACTERIOLOGY
1. O antigens and biochemicals define four species Shigella dysenteriae
(serogroup A), Shigella flexneri (serogroup B), Shigella boydii (serogroup C), and
Shigella sonnei (serogroup D)
2. All but S. sonnei are further subdivided into a total of 38 individual O antigen
serotypes specified by numbers
3. Invasiveness and Stx production are virulence factors
II. SHIGELLOSIS
A. EPIDEMIOLOGY
1. Strictly human disease
2. Low infecting dose facilitates fecal–oral spread person-to-person
3. Personal and community sanitary practices determine incidence
4. Wars and natural disasters create outbreaks
B. PATHOGENESIS
1. Bacteria pass stomach acid and invade colon
2. Transcytose M cells to macrophages
3. Invade enterocytes from dead macrophages
4. Injected invasion plasmid antigens (IpaA, IpaB, IpaC) induce endocytosis
5. Escape phagosome to cytoplasm
6. Polymerization of cytoskeletal actin propels bacteria through cytoplasm
7. Microtubules are digested
8. Adjacent enterocytes are invaded directly
9. Double-membrane lysis restarts process in new cell
10 Enterocyte invasion creates ulcers in colonic mucosa
11. Diarrhea + WBCs + RBCs = dysentery
12. Stx increases severity of disease
13. Large plasmid containing Ipa genes is required for virulence
III. SHIGELLOSIS: CLINICAL ASPECTS
A. MANIFESTATIONS
1. Watery diarrhea is followed by fever, bloody mucoid stools, and cramping
2. Mortality significant with S. dysenteriae type 1
3. Most infections are self-limiting
B. DIAGNOSIS
1. Selective media are routinely used in clinical laboratory stool cultures
2. O antigen agglutination tests confirm species
C. TREATMENT
1. TMP-SMX, fluoroquinolones, ceftriaxone, azithromycin, or nalidixic acid
treatment shortens illness and excretion
2. Ampicillin resistance is common
PREVENTION
1. Sanitation, insect control, handwashing, and cooking block transmission
2. Live attenuated vaccines are under investigation
Salmonella
I. BACTERIOLOGY
1. Complexity of O, K, and H antigens leads to many serotypes
2. Historic species names persist as serotypes of S. enterica
3. Salmonella species vary in preferred host
4. S. enterica serovar Typhi infects only humans
5. Type 1 pili and flagella present
II. SALMONELLA GASTROENTERITIS (S. enterica)
A. EPIDEMIOLOGY
1. Improper food handling allows the transmission from the animal reservoir to
humans
2. Infecting dose is much higher than Shigella making person-to-person spread
unlikely
3. Bacteria increase their numbers by growth in contaminated foods prior to
ingestion
4. Poultry products are common source
5. Outbreaks in institutions are common
6. Human carriers can be a source
7. Modern delivery systems can spread disease efficiently in multistate outbreaks
B. PATHOGENESIS
1. Adherence to enterocyte triggers surface “ruffles”
2. Secretion system genes are in PAIs
3. Ruffles induce endocytosis
4. Bacteria progress through cell to lamina propria
5. Macrophage apoptosis aids survival in submucosa
6. Enterotoxin role is unclear
7. Invasion and inflammation cause diarrhea
III. ENTERIC (TYPHOID) FEVER (Salmonella serovar
Typhi)
A. EPIDEMIOLOGY
1. Cases are always traceable to a human source
2. Fecal–oral transmission requires moderate dose
3. Prevalence is linked to sanitary infrastructure
B. PATHOGENESIS
1. Typhi invades M cells and macrophages
2. Vi surface polysaccharide limits PMN phagocytosis
3. Macrophage oxidative burst inhibited
4. Infection spreads through reticuloendothelial system (RES)
5. RES sites seed the bloodstream and other organs
6. Endotoxin produces the fever of typhoid
C. IMMUNITY
1. TH1 and TH2 mediated immunity follows natural infection
IV. SALMONELLOSIS: CLINICAL ASPECTS
A. MANIFESTATIONS
a. Gastroenteritis
1. S. enterica = gastroenteritis
2. Diarrhea, vomiting, and cramps are common
b. Bacteremia and Metastatic Infection
1. Bacteremia is most common and severe in immunocompromised
2. Metastatic sites linked to previous injury particularly sickle-cell
c. Enteric Fever – S. Typhi = enteric fever
1. Multiorgan system infection characterized by prolonged fever, sustained
bacteremia, and involvement of lymph nodes, liver, and spleen
2. Slowly increasing fever lasts for weeks
3. Diarrhea is intermittent or absent
4. Bacteremia leads to biliary tree infection which in turn reseeds intestine
5. Urinary tract, bone, and joints are metastatic sites
B. DIAGNOSIS
1. Stool and blood culture are routine
2. Early in the course of enteric fever, blood is far more likely to give a positive
culture result than culture from any other site including stool
3. Typhi has characteristic bacteriologic features
C. TREATMENT
1. The primary therapeutic approach to Salmonella gastroenteritis is fluid and
electrolyte replacement and the control of nausea and vomiting
2. Antimicrobics are of limited use in gastroenteritis
3. In typhoid fever antibiotics are effective but resistance is common
D. PREVENTION
1. Typhoid vaccines are only moderately effective
2. Sanitation and public health measures can eliminate Typhi
YERSINIA
I. BACTERIOLOGY
1. Coccobacillary and grow at variable temperatures
2. Human pathogens linked to animals
II. YERSINIA DISEASES (Y. pseudotuberculosis and Y.
enterocolitica)
A. EPIDEMIOLOGY
1. Transmitted by ingestion from animal source
2. Geographic variation is great
B. PATHOGENESIS
1. Intestinal M cells are invaded
2. Injected major effector proteins called Yops disrupt cellular function
3. Ca2+ and temperature regulate virulence factor expression
4. Plasmid and PAI contain virulence genes
5. Spread leads to microabscesses in lymph nodes
6. Y. pestis reaches the dermal lymphatics by the bite of an infected flea
7. Y. pestis has capsule, plasminogen activator, and fibrinolysin
III. YERSINIA INFECTIONS: CLINICAL ASPECTS
1. Mesenteric lymphadenitis creates abdominal pain
2. Yersinia are not routinely sought in stool cultures
3. Antimicrobics have variable effect
OTHER ENTEROBACTERIACEAE
I. KLEBSIELLA
1. Polysaccharide capsule blocks complement deposition
2. Klebsiella species are now among the most resistant to antimicrobics.
II. ENTEROBACTER
1. Modest virulence but are linked to hospital contamination
III. SERRATIA
1. Red pigment (in culture) and multiresistance are characteristic
IV. CITROBACTER
1. Uncommon cause of opportunistic infection and brain abscess
I. PROTEUS, PROVIDENCIA, AND MORGANELLA
1. Swarming over agar plates is a feature of some species
2. Urease production is linked to urinary stones