Table 1.
Virulence-associated traits of extraintestinal pathogenic Escherichia coli (ExPEC) by functional categorya
| Category | Gene(s) or operon | Comment | Evidence for trait as a virulence factor (reference[s]) | |
|---|---|---|---|---|
| Epidemiologicalb | Experimental (in vivo)c | |||
| Adhesinsd | afa/dra | Dr antigen-binding adhesins (AFA I-III, Dr, F1845) | Yes (176, 266, 267) | Yes (268) |
| afaE-8 | Afimbrial adhesin VIII | Yes (175) | No | |
| auf | Surface structure of unclear function | Yes (269) | No (269) | |
| bmaE | Blood group M-specific adhesin | Yes (270) | No | |
| clpG | CS31A adhesin (K88–related) | Yes (271) | No | |
| csgA | Curli | Yes (272) | Yes (272) | |
| ecp | Pilus | Yes (273) | No | |
| fim | D-mannose-specific adhesin, type-1 fimbriae | Yes (267, 274, 275) | Yes (89, 276) | |
| foc | F1C fimbriae | Yes (277) | No | |
| gafD | GlcNac-specific (G, F17c) fimbriae adhesin | Yes (270, 271) | No | |
| iha | Iron-regulated-gene-homologue adhesin | Yes (21, 111, 267) | Yes (96) | |
| nfa | NFA-1, -2, -3, -4 (nonfimbrial adhesins) | No (278–280) | No | |
| pap | Pilus associated with pyelonephritis (P fimbriae) | Yes (9, 151, 267) | Yes (281); no (282) | |
| pil | Type IV pilus | Yes (283) | Yes (284) | |
| sfa | S fimbriae (sialic acid-specific) | Yes (111) | Yes (285) | |
| sfa/foc | S and F1C fimbriae | Yes (286) | Yes (285) | |
| yad | Fimbria | Yes (283) | Yes (283) | |
| ygi | Fimbria | Yes (283) | Yes (283) | |
| yvc | Fimbria | Yes (283) | No | |
| Toxinsd | astA | EAST1, heat-stable enteroaggregative E. coli cytotoxin | Yes (79, 287) | No (189, 288) |
| cdtB | Cytolethal distending toxin, CDT | Yes (111) | No | |
| cnf1 | Cytotoxic necrotizing factor 1, CNF-1 | Yes (289) | Yes (98, 290, 291) | |
| hly | α-Hemolysin (Hly) | Yes (292) | Yes (100, 293) | |
| pic | Protein associated with intestinal colonization, PIC | Yes (294) | Yes (18, 284, 294, 295) | |
| sat | Secreted autotransporter toxin (serine protease) | Yes (20, 267) | Yes (296) | |
| tsh | Temperature-sensitive hemagglutinin, TSH | Yes (68, 294) | Yes (18, 294) | |
| upxA (tosA) | RTX toxin | Yes (297) | Yes (298) | |
| vat | Vacuolating autotransporter toxin | Yes (299, 300) | Yes (284) | |
| Nutrition | argC | Arginine synthesis | N/Ae | Yes (301) |
| aro | Shikimate synthesis | N/Ae | Yes (284) | |
| chuA | Heme receptor | Yes (268) | Yes (97) | |
| dppA-oppA-sapA | Uptake of short peptides and amino acids | Yes (284, 302) | ||
| dsd | Serine utilization | Yes (303) | No (304) | |
| entF | Enterobactin synthesis | No | Yes (65) | |
| fyuA, irp | Yersiniabactin (siderophore) receptor, synthesis | Yes (122, 267, 268) | Yes (305) | |
| guaA | Guanine synthesis | N/Ae | Yes (301) | |
| ireA | Iron-regulated element (catecholate siderophore) | Yes (23) | Yes (23) | |
| iroN | Salmochelin (siderophore) receptor | Yes (21, 306) | Yes (65, 95) | |
| iuc, iutA | Aerobactin (siderophore) synthesis, receptor | Yes (268, 307) | Yes (97) | |
| pckA | Gluconeogenesis | Yes (302) | ||
| sdhB | TCA cycle | Yes (302) | ||
| tonB | Siderophore uptake | N/Ae | Yes (65) | |
| Protectins | iss | Increased serum survival (outer membrane protein) | Yes (307, 308) | Yes (309) |
| kpsMT II | Group II capsule synthesis (e.g., K1, K5, K12) | Yes (112, 126, 267, 310) | Yes (311) | |
| kpsMT III | Group III capsule synthesis (e.g., K3, K10, K54) | Yes (112, 126, 310) | Yes (312) | |
| proP | Osmoprotection; proline permease | N/Ae | Yes (313) | |
| rfc | O4 lipopolysaccharide (LPS) synthesis | Yes (314, 315) | Yes (316) | |
| traT | Surface exclusion; serum resistance-associated | Yes (307) | No (317) | |
| TCSSf | barA-uvrY | Regulation of VFs, e.g., hemolysin, LPS | Yes (318) | |
| cpxAR | Regulation of VFs, e.g., hemolysin | Yes (319) | ||
| envZ-ompR | Regulation of VFs, e.g., osmoprotection | Yes (320) | ||
| kguRS | Regulation of VFs, e.g., nutrient acquisition | Yes (321) | Yes (321) | |
| qseBC | Regulation of VFs, e.g., adhesins, flagella | Yes (322) | ||
| Invasins | aslA | Cellular invasion (arylsulfatase-like gene) | N/Ae | Yes (323) |
| ibeA-C | Invasion of brain endothelium IbeA (Ibe10), B, and C | Yes (IbeA) (111) | Yes (323) | |
| nlpI | Invasion of brain endothelium, complement resistance | No | Yes (324, 325) | |
| ompA | Outer membrane protein A (cellular invasion) | N/Ae | Yes (323) | |
| traJ | Cellular invasion (F-like plasmid transfer region homologue) | No | Yes (323) | |
| Misc.g | cvaC | Microcin (colicin) V; on plasmids with traT, iss, iuc/iut | Yes (307) | Yes (326) |
| fliC | Flagella: motility, ascent to the kidneys | Yes (327) | ||
| malX | Pathogenicity island marker (from strain CFT073) | Yes (130, 132, 267) | No (139) | |
| ompT | Outer membrane protein T (protease) | Yes (328) | Yes (unpublished, JRJ) | |
| pga | Extracellular polysaccharide (poly-GlcNac), biofilm | Yes (284) | ||
| rfaH | Transcriptional antitermination: O antigen, capsule, Hly, ChuA | Yes (329) | ||
| usp | Uropathogenic-specific protein (bacteriocin) | Yes (22, 120, 267) | Yes (330) | |
| ydd-pqq | ABC transporter, inner-outer membrane proteins | Yes (284) | ||
Note: list is not comprehensive even for recognized markers, and additional markers remain to be identified and characterized. Conversely, not all the listed traits necessarily contribute to virulence; some are only epidemiologically linked with virulence or confer in vitro phenotypes that are suspected of promoting virulence. Additionally, some of the listed traits are prominent also among intestinal pathogenic E. coli, e.g., cytolethal distending toxin, certain Dr-binding adhesins, and EAST1 (astA).
Statistically associated with clinical isolates or specific host characteristics, or highly prevalent in a particular extraintestinal infection syndrome.
Based on animal model infection studies, not necessarily using isogenic strains or complemented mutants.
Certain adhesins and toxins function as invasins, e.g., type-1 fimbriae, some Dr-binding adhesins, and CNF-1 (115, 145, 197).
N/A, not applicable (ubiquitous within E. coli, which precludes epidemiological comparisons).
TCSS, two-component secretion system.
Misc., miscellaneous.