Enetrobacteriaceae I Flashcards
Enterobacteriaceae Family
•Escherichia coli, Shigella, Salmonella, Klebsiella, Enterobacter, Serratia, Proteus, Morganella, Providencia
Enterobacteriaceae Family Diseases
Urinary tract infection, watery diarrhea, dysentery, enteric fever, wound and soft tissue infections
General Features of Enterobacteriaceae: Structure
The Enterobacteriaceae are among the largest bacteria; producing forms that range from large coccobacilli to elongated, filamentous rods.
- Gram -
- Facultative anaerobes
- The outer membrane lipopolysaccharide (LPS) is called the O antigen. Its antigenic specificity is determined by the composition of the sugars that form the long terminal polysaccharide side chains
- Cell-surface polysaccharides may form a well-defined capsule or an amorphous slime layer and are termed the K antigen
- Motile strains have protein peritrichous flagella, which extend well beyond the cell wall and are called the H antigen.
- Surface pili are antigenic proteins but not part of any formal typing scheme.
General Features of Enterobacteriaceae: Growth and Metabolism
•Enterobacteriaceae grow readily on simple media, often with only a single carbon energy source. Growth is rapid under both aerobic and anaerobic conditions.
General Features of Enterobacteriaceae: Classification
Genus and species designations are based on phenotypic characteristics, such as patterns of carbohydrate fermentation.
- O, K, and H antigens are used to further divide some species into multiple serotypes.
- Genera containing the species most virulent for humans are Escherichia, Shigella, Salmonella, Klebsiella, and Yersinia (discussed separately under bacterial zoonoses)
- Less common but still medically important genera are Enterobacter, Serratia, Proteus, Morganella, and Providencia.
Diseases Caused by Enterobacteriaceae
Most Enterobacteriaceae are primarily members of the lower gastrointestinal microbiota of humans and animals. Many survive readily in nature, and are found living free anywhere water and minimal energy sources are available. In humans they are the major facultative component of the colonic microbiota.
- E. coli is the most common species
- Salmonella and Shigella species are enteric pathogens and not considered members of the resident intestinal microbiota.
Diseases Caused by Enterobacteriaceae Opportunistic Infections
•Enterobacteriaceae are often poised to take advantage of their common presence in the environment and microbiota to produce disease when they gain access to normally sterile body sites.
Diseases Caused by Enterobacteriaceae Diarrhea
Salmonella, Shigella, Yersinia enterocolitica, and certain strains of E. coli are able to produce disease in the intestinal tract. These intestinal pathogens have invasive properties or virulence factors such as cytotoxins and enterotoxins which correlate with the type of diarrhea they produce.
- Invasive and cytotoxic strains produce an inflammatory diarrhea called dysentery with WBCs and/or blood in the stool.
- Enterotoxin producing strains produce a watery diarrhea in which fluid loss is the primary pathophysiologic feature.
- For a few species the intestinal tract is the portal of entry but the disease is a systemic syndrome called enteric fever
Diseases Caused by Enterobacteriaceae Manifestations
The Enterobacteriaceae produce the widest variety of infections of any group of microbial agents including two of the most common infectious states, urinary tract infection and acute diarrhea.
Diseases Caused by Enterobacteriaceae Treatment
Antimicrobial therapy is crucial to the outcome of infections with members of the Enterobacteriaceae. Unfortunately, combinations of chromosomal and plasmid-determined resistance render them the most variable of all bacteria in susceptibility to antimicrobial agents. Susceptibility of any individual strain must be determined by in vitro tests which are readily available.
E. coli Pili
Pili are usually present on the surface of E. coli strains and some have been shown to play a role in virulence as mediators of attachment to human epithelial surfaces.
- Type 1 (common) pili bind to the D-mannose residues present on a wide variety of epithelial cell surfaces
- Specialized pili mediate binding only to certain cell types.
-The most important are P pili which bind to moieties present on kidney cells, and pili of diarrhea-causing E. coli which bind to human enterocytes
E. coli Toxins
- alpha hemolysin
- Shiga Toxin
- Labile Toxin
- Stable Toxin
E. coli Alpha Hemolysin
Alpha hemolysin is a pore-forming cytotoxin which inserts into the plasma membrane of a wide range of host cells in a manner similar to streptolysin O.
E. coli Shiga Toxin
Shiga toxin (Stx) is an A/B toxin released by certain E. coli and Shigella strains upon lysis of the bacteria
- B unit directs binding to a specific glycolipid receptor (Gb3) present on eukaryotic cells and is internalized in an endocytotic vacuole.
- The A subunit crosses the vacuolar membrane in the trans-Golgi network, enzymatically modifies sites on a ribosomal RNA subunit (60S). This prevents binding of amino acyl tRNA to the ribosome, blocking protein synthesis
E. coli Labile Toxin
Labile toxin (LT) is also an A/B toxin. Its name relates to the physical property of heat lability.
- B subunits bind to the cell membrane and the A subunit catalyzes the ADP-ribosylation of a regulatory G protein (like cholera toxin).
- LT structure and action are nearly identical to CT but LT is less potent
- Causes activation of the membrane associated adenylate cyclase system
- Result is the stimulation of chloride secretion out of the cell causing accumulation of water and electrolytes into the bowel lumen.
E. coli Stable Toxin
Stable toxin (ST) toxins bind to a glycoprotein receptor, resulting in the activation of a membrane-bound guanylate cyclase. The resulting increase in cyclic GMP concentration causes an LT-like net secretion of fluid and electrolytes into the bowel lumen.
E. coli UTI Epidemiology
E. coli accounts for more than 90% of the millions of UTI cases estimated to occur every year.
- UTI is most common in women during the sexually active years.
- The reservoir is the patient’s own intestinal E. coli flora.
- UTI in men UTI increases later in life in association with conditions causing urinary obstruction such as prostatic hypertrophy.
-E. coli is still common but other Enterobacteriaceae and bacterial species enter the picture as well.
E. coli UTI Pathogenesis
Relatively minor trauma or the mechanical disruption of sexual intercourse allows bacteria access to the bladder. In most instances these bacteria are purged by the flushing action of voiding. The ability of uropathic E. coli (UPEC) to produce UTI is related to general virulence factors together with pili-mediated adherence to uroepithelial cells.
- Type 1 pili bind uroepithelial cells and are additionally important by aiding in periurethral colonization as the prelude to bladder access.
- P pili bind to a digalactoside (Gal-Gal) receptor which is present on uroepithelial cells in the upper urinary tract and kidney. P pili avidly bind UPEC to these cells.
- Motility mediated by flagella facilitates E. coli access to the bladder and upper urinary tract. UPEC are able to shift between adherent and motile phases.
- UPECs can also invade superficial epithelial cells, a feature felt to resist the flushing action of voiding.
Factors that violate bladder integrity (urinary catheters) or that obstruct urine outflow (enlarged prostate) enhance the probability of infection.
E. coli Intestinal Infections
Diarrhea-causing E. coli are classified according to their virulence properties as
- enterotoxigenic (ETEC),
- enteropathogenic (EPEC),
- enteroinvasive (EIEC),
- enterohemorrhagic (EHEC) or
- enteroaggregative (EAEC).
•Each group causes disease by a different mechanism, and the resulting syndromes usually differ clinically and epidemiologically.
ETEC Epidemiology
ETEC are the most important cause of “travelers’ diarrhea” in visitors to less developed countries. ETEC also produce diarrhea in infants native to these countries where they are a leading cause of morbidity and mortality during the first 2 years of life.
- Transmission is by consumption of food and water contaminated by human cases or convalescent carriers
- Direct person-to-person transmission is unusual because the infecting dose is high.
ETEC Pathogenesis
ETEC diarrhea is caused by strains of E. coli which produce LT, ST, or both enterotoxins in the small intestine.
- Adherence to surface microvilli mediated by colonizing factor (CF) pili is essential for the efficient delivery of toxin to the target enterocytes.
- The genes encoding ST, LT, and the CF pili are borne in plasmids. All three may be on the same plasmid
EPEC Epidemiology
In less developed countries all over the world EPEC account for up to 20% of diarrhea in bottle-fed infants below 1 year of age. The reservoir is infant cases and adult carriers with transmission by the fecal-oral route.
EPEC Pathogenesis
EPEC initially attach to enterocytes utilizing bundle-forming pili (Bfp) which form clustered microcolonies on the enterocyte cell surface. The lesion then progresses with effacement of the microvilli and changes in the cell morphology including the production of dramatic “pedestals” with the EPEC bacterium at their apex. The combination of these actions is called the attachment and effacing (A/E) lesion.
- Intimin is major attachment protein
- A type III secretion system injects at least five E. coli secretion proteins (Esps) into the host cell cytoplasm
- The receptor for intimin is also injected
- Esps perturb intracellular signal transduction pathways
- Modifications in enterocyte cytoskeleton proteins create the A/E lesion
EHEC Epidemiology
EHEC disease and its accompanying hemolytic uremic syndrome (HUS) are the result of consumption of products from animals colonized with EHEC strains. Most cases are linked to a single E. coli serotype, O157:H7
- Important cause of bloody diarrhea in industrialized nations
- Some cases develop HUS with hemolytic anemia, renal failure, and thrombocytopenia
- Regional and national outbreaks have been associated with undercooked hamburger and unpasteurized juices.
The emergence of EHEC is related to its virulence, low infecting dose, common reservoir (cattle), and changes in the modern food processing industry that provide us with fresher meat (and bacteria). The low infecting dose, estimated at 100 – 200 organisms, is particularly important and can lead to person-to-person transmission.
- Modern meat processing plants can mix EHEC from colonized cattle at one ranch into beef from hundreds of other farms
- Infecting dose of EHEC may remain even after cooking if hamburger is left rare in the middle.
- Unpasteurized milk, fruits, and vegetables have also been the source when the manure of cattle grazing nearby has contaminated them in the field.
