Uropathogenic strains of Escherichia coli are characterized by the expression of distinctive bacterial properties, products, or structures referred to as virulence factors because they help the organism overcome host defenses and colonize or invade the urinary tract. Virulence factors of recognized importance in the pathogenesis of urinary tract infection (UTI) include adhesins (P fimbriae, certain other mannose-resistant adhesins, and type 1 fimbriae), the aerobactin system, hemolysin, K capsule, and resistance to serum killing. This review summarizes the virtual explosion of information regarding the epidemiology, biochemistry, mechanisms of action, and genetic basis of these urovirulence factors that has occurred in the past decade and identifies areas in need of further study. Virulence factor expression is more common among certain genetically related groups of E. coli which constitute virulent clones within the larger E. coli population. In general, the more virulence factors a strain expresses, the more severe an infection it is able to cause. Certain virulence factors specifically favor the development of pyelonephritis, others favor cystitis, and others favor asymptomatic bacteriuria. The currently defined virulence factors clearly contribute to the virulence of wild-type strains but are usually insufficient in themselves to transform an avirulent organism into a pathogen, demonstrating that other as-yet-undefined virulence properties await discovery. Virulence factor testing is a useful epidemiological and research tool but as yet has no defined clinical role. Immunological and biochemical anti-virulence factor interventions are effective in animal models of UTI and hold promise for the prevention of UTI in humans. Images

Virulence factors in Escherichia coli urinary tract infection.

The actin cytoskeleton is regulated by GTP-hydrolysing proteins, the Rho GTPases, which act as molecular switches in diverse signal-transduction processes Various bacterial toxins can inactivate Rho GTPases by ADP-ribosylation or glucosylation Previous research has identified Rho proteins as putative targets for Escherichia coli cytotoxic necrotizing factors 1 and 2 (CNF1 and 2) These toxins induce actin assembly and multinucleation in culture cells Here we show that treatment of RhoA with CNF1 inhibits the intrinsic GTPase activity of RhoA and completely blocks GTPase activity stimulated by the Rho-GTPase-activating protein (rhoGAP) Analysis by mass spectrometry and amino-acid sequencing of proteolytic peptides derived from CNF1-treated RhoA indicate that CNF1 induces deamidation of a glutamine residue at position 63 (Gln 63) to give constitutively active Rho protein

Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1

https://mmbr.asm.org/content/mmbr/60/1/167.full.pdf

Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion.

Pathogenic Escherichia coli are responsible for a variety of diseases, including diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the virulence factors produced by uropathogenic (CNF1)1 or enteropathogenic (CNF2)2 E. coli strains that cause diseases in humans and animals, respectively. CNFs induce an increase in the content of actin stress fibres and focal contacts in cultured cells3,4. Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho4,5 and indirect evidence indicates that CNF1 might constitutively activate Rho6. Here we show that CNF1 catalyses the deamidation of a glutamine residue at position 63 of Rho, turning it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the reorganization of actin stress fibres. To our knowledge, CNF1 is the first example of a bacterial toxin acting by deamidation of a specific target protein.

/pdf/toxin-induced-activation-of-the-g-protein-p21-rho-by-53z84e3t09.pdf

Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine

Members of the genus Shigella are phenotypically similar to Escherichia coli and, with the exception of Shigella boydii serotype 13, would be considered the same species by DNA-DNA hybridization analysis and whole-genome sequence analysis. The dynamic nature of the Shiga toxin-converting phages has implications for diagnostic testing for Shiga toxin-producing E. coli (STEC). Since STEC strains can lose critical virulence genes, some researchers have proposed that multiple virulence-associated genes, as well as conserved genes, be used to diagnose infections by these bacteria. This concept would also apply to other pathotypes of E. coli, as most of them carry critical virulence genes on mobile genetic elements. A preliminary report can be issued as soon as a presumptive identification of Salmonella is obtained. In most situations, a presumptive identification is based on phenotypic traits determined by either traditional or commercial systems or by reactivity with Salmonella O grouping antisera. A confirmed identification requires both phenotypic identification and O group or serotype determination. As national surveillance systems depend on the receipt of serotype information for Salmonella strains isolated in the United States, laboratories should follow the procedures recommended by their state health departments for submitting Salmonella isolates for further characterization, including complete serotyping. The antimicrobial susceptibilities of typhoidal Salmonella strains and strains from normally sterile sites should be determined, and the strains should be forwarded to a reference or public health laboratory for complete phenotypic identification and serotyping.

Escherichia, Shigella, and Salmonella

A factor produced by several strains of Escherichia coli isolated from enteritis-affected children has been shown to produce both a necrotizing effect on rabbit skin and striking morphological alterations on CHO, Vero, and HeLa cells. The same strains were found to have hemolytic activity on sheep erythrocytes. The toxic, cell-altering factor was demonstrated to be different from both heat-labile and heat-stable enterotoxins and from Vero toxin. The main effect induced by the isolated factor on cultured cells was the formation of large multinucleated cells. The partial purification achieved suggests that the same factor (most likely a protein with a molecular weight of 70,000 to 80,000) is responsible for toxic and cell-altering activities, whereas a different molecular species is responsible for hemolytic activity.

L G Roda

Papers

Partial purification and characterization of an escherichia coli toxic factor that induces morphological cell alterations.