Few microorganisms are as versatile as Escherichia coli. An important member of the normal intestinal microflora of humans and other mammals, E. coli has also been widely exploited as a cloning host in recombinant DNA technology. But E. coli is more than just a laboratory workhorse or harmless intestinal inhabitant; it can also be a highly versatile, and frequently deadly, pathogen. Several different E. coli strains cause diverse intestinal and extraintestinal diseases by means of virulence factors that affect a wide range of cellular processes.
In addition to being an important member of the normal intestinal microflora of humans and other mammals, the species Escherichia coli contains many pathotypes that cause a variety of diseases. At least six different pathotypes cause enteric disease, such as diarrhoea or dysentery, and other pathotypes cause extra-intestinal infections, including urinary tract infections and meningitis.
Virulence factors of E. coli can affect a wide range of eukaryotic cellular processes, including cell signalling, ion secretion, protein synthesis, mitosis, cytoskeletal function and mitochondrial function.
Virulence factors of pathogenic E. coli are frequently encoded on genetic elements such as plasmids, bacteriophage, transposons and pathogenicity islands that can be mobilized into different strains to create novel combinations of virulence factors.
The genomic structure of the E. coli pathotypes that have been sequenced so far show a striking mosaic pattern, with 2,000 genes present in 247 islands in one pathotype that are not present in K-12. Up to 0.53 MB of DNA present in K-12 can also be absent from pathogenic E. coli.
Genes that encode virulence factors of pathogenic E. coli are regulated by both pathotype-specific regulators that are absent from commensal E. coli, and by 'housekeeping' regulators that are present in commensal E. coli.
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Work in the authors' laboratories is supported by the National Institutes of Health. We thank J. Girón for providing electron micrographs. We apologize to the numerous investigators whose papers could not be cited due to space constraints.
The Protein Data Bank
A group of strains of a single species that cause a common disease using a common set of virulence factors.
An antigenically distinct variety of serotype, based only on O (LPS) antigens.
An antigenically distinct variety within a bacterial species. For E. coli, a specific combination of O (lipopolysaccharide), H (flagellar) and sometimes K (capsular) antigens defines a serotype.
- DECAY-ACCELERATING FACTOR
(DAF). A plasma membrane protein, also called CD55, that regulates the complement cascade by interfering with the formation of the C3bBb complex.
A homologue of MHC (major histocompatibility complex) I molecules. Two homologues have been described called MICA (MHC class I chain-related gene A) and MICB (MHC class I chain-related gene B).
- TH1 IMMUNE RESPONSE
A response that is characterized by a subset of helper T cells that secrete a particular set of cytokines, including IL-2, interferon-γ and TNF-α, the main function of which is to stimulate phagocytosis-mediated defences against intracellular pathogens.
A nucleolar protein that functions as a shuttle protein between the nucleus and the cytoplasm and is also found on the cell surface.
GTPase-activating protein. A family of eukaryotic proteins that modulate the activity of Rac, Rho and Cdc42.
A neuropeptide that is widely distributed in the central nervous system and the gastrointestinal tract. Binding to the galanin-1 receptor can alter intestinal ion flux.
- USSING CHAMBER
A device that is used to measure ion flow across an epithelium. Bacterial enterotoxins that induce ion fluxes are frequently studied in Ussing chambers.
- SIGNATURE-TAGGED MUTAGENESIS
(STM). A technique to screen large numbers of distinct mutants for those that fail to survive an animal infection. Each mutant is tagged with a unique DNA sequence (called a signature tag), which allows a specific mutant to be tracked within a large pool of bacteria.
In vivo expression technology is a promoter trap technique that uses cloned promoters fused to a reporter gene. A library of such constructs is introduced into an animal model to detect promoters that are activated in vivo.
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