Abstract
Group 2 capsules and lipopolysaccharides are regarded as important virulence factors in extraintestinal isolates of Escherichia coli, but their specific contributions to bladder and renal infections, if any, are unknown. Proven isogenic derivatives deficient in the K54 antigen alone (CP9.137), the O4 antigen alone (CP921), or both the K54 and O4 antigens (CP923) were compared with their wild-type parent (CP9 [O4/K54JH5]) for growth in human urine in vitro and for virulence in vivo in a mouse model of ascending urinary tract infection (UTI). Growth of CP9.137 and CP921 was equivalent to that of CP9 in human urine. CP923 demonstrated a small but reproducible decrease in log-phase growth but achieved the same plateau density. In the mouse model of UTI, the isogenic mutant deficient in the 04 antigen alone (CP921) and, to a greater degree, the derivative deficient in both the K54 and O4 antigens (CP923) were significantly less virulent in nearly all parameters measured. In contrast, the K54 knockout derivative was as virulent as its parent, CP9, in causing bladder infection and nearly as virulent in causing renal infection. These results demonstrate an important role for the O4 antigen moiety of lipopolysaccharide in the pathogenesis of UTI. The possibility that the K54 antigen also plays a minor role cannot be excluded.
Full Text
The Full Text of this article is available as a PDF (250.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Acquatella H., Little P. J., de Wardener H. E., Coleman J. C. The effect of urine osmolality and pH on the bactericidal activity of plasma. Clin Sci. 1967 Dec;33(3):471–480. [PubMed] [Google Scholar]
- Allen P. M., Roberts I., Boulnois G. J., Saunders J. R., Hart C. A. Contribution of capsular polysaccharide and surface properties to virulence of Escherichia coli K1. Infect Immun. 1987 Nov;55(11):2662–2668. doi: 10.1128/iai.55.11.2662-2668.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BEESON P. B., ROWLEY D. The anticomplementary effect of kidney tissue; its association with ammonia production. J Exp Med. 1959 Nov 1;110:685–697. doi: 10.1084/jem.110.5.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHERNEW I., BRAUDE A. I. Depression of phagocytosis by solutes in concentrations found in the kidney and urine. J Clin Invest. 1962 Oct;41:1945–1953. doi: 10.1172/JCI104652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross A. S., Gemski P., Sadoff J. C., Orskov F., Orskov I. The importance of the K1 capsule in invasive infections caused by Escherichia coli. J Infect Dis. 1984 Feb;149(2):184–193. doi: 10.1093/infdis/149.2.184. [DOI] [PubMed] [Google Scholar]
- Cross A. S., Kim K. S., Wright D. C., Sadoff J. C., Gemski P. Role of lipopolysaccharide and capsule in the serum resistance of bacteremic strains of Escherichia coli. J Infect Dis. 1986 Sep;154(3):497–503. doi: 10.1093/infdis/154.3.497. [DOI] [PubMed] [Google Scholar]
- Cross A. S. The biologic significance of bacterial encapsulation. Curr Top Microbiol Immunol. 1990;150:87–95. doi: 10.1007/978-3-642-74694-9_5. [DOI] [PubMed] [Google Scholar]
- Domingue G. J., Laucirica R., Baliga P., Covington S., Robledo J. A., Li S. C. Virulence of wild-type E. coli uroisolates in experimental pyelonephritis. Kidney Int. 1988 Dec;34(6):761–765. doi: 10.1038/ki.1988.246. [DOI] [PubMed] [Google Scholar]
- Ge Y., Ezzell R. M., Tompkins R. G., Warren H. S. Cellular distribution of endotoxin after injection of chemically purified lipopolysaccharide differs from that after injection of live bacteria. J Infect Dis. 1994 Jan;169(1):95–104. doi: 10.1093/infdis/169.1.95. [DOI] [PubMed] [Google Scholar]
- Hagberg L., Engberg I., Freter R., Lam J., Olling S., Svanborg Edén C. Ascending, unobstructed urinary tract infection in mice caused by pyelonephritogenic Escherichia coli of human origin. Infect Immun. 1983 Apr;40(1):273–283. doi: 10.1128/iai.40.1.273-283.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hitchcock P. J., Brown T. M. Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels. J Bacteriol. 1983 Apr;154(1):269–277. doi: 10.1128/jb.154.1.269-277.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jann K., Jann B. Polysaccharide antigens of Escherichia coli. Rev Infect Dis. 1987 Sep-Oct;9 (Suppl 5):S517–S526. doi: 10.1093/clinids/9.supplement_5.s517. [DOI] [PubMed] [Google Scholar]
- Johnson J. R., Berggren T., Manivel J. C. Histopathologic-microbiologic correlates of invasiveness in a mouse model of ascending unobstructed urinary tract infection. J Infect Dis. 1992 Feb;165(2):299–305. doi: 10.1093/infdis/165.2.299. [DOI] [PubMed] [Google Scholar]
- Johnson J. R., Berggren T., Newburg D. S., McCluer R. H., Manivel J. C. Detailed histopathological examination contributes to the assessment of Escherichia coli urovirulence. J Urol. 1992 Apr;147(4):1160–1166. doi: 10.1016/s0022-5347(17)37507-9. [DOI] [PubMed] [Google Scholar]
- Johnson J. R., Brown J. J. Defining inoculation conditions for the mouse model of ascending urinary tract infection that avoid immediate vesicoureteral reflux yet produce renal and bladder infection. J Infect Dis. 1996 Mar;173(3):746–749. doi: 10.1093/infdis/173.3.746. [DOI] [PubMed] [Google Scholar]
- Johnson J. R., Lyons M. F., 2nd, Pearce W., Gorman P., Roberts P. L., White N., Brust P., Olsen R., Gnann J. W., Jr, Stamm W. E. Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days. J Infect Dis. 1991 Feb;163(2):325–330. doi: 10.1093/infdis/163.2.325. [DOI] [PubMed] [Google Scholar]
- Johnson J. R. Virulence factors in Escherichia coli urinary tract infection. Clin Microbiol Rev. 1991 Jan;4(1):80–128. doi: 10.1128/cmr.4.1.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Joiner K. A. Complement evasion by bacteria and parasites. Annu Rev Microbiol. 1988;42:201–230. doi: 10.1146/annurev.mi.42.100188.001221. [DOI] [PubMed] [Google Scholar]
- Kaijser B., Hanson L. A., Jodal U., Lidin-Janson G., Robbins J. B. Frequency of E. coli K antigens in urinary-tract infections in children. Lancet. 1977 Mar 26;1(8013):663–666. doi: 10.1016/s0140-6736(77)92111-0. [DOI] [PubMed] [Google Scholar]
- Kaijser B. Immunology of Escherichia coli: K antigen and its relation to urinary-tract infection. J Infect Dis. 1973 Jun;127(6):670–677. doi: 10.1093/infdis/127.6.670. [DOI] [PubMed] [Google Scholar]
- Kalmanson G. M., Harwick H. J., Turck M., Guze L. B. Urinary-tract infection: localisation and virulence of Escherichia coli. Lancet. 1975 Jan 18;1(7899):134–136. doi: 10.1016/s0140-6736(75)91430-0. [DOI] [PubMed] [Google Scholar]
- Kim K. S., Itabashi H., Gemski P., Sadoff J., Warren R. L., Cross A. S. The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat. J Clin Invest. 1992 Sep;90(3):897–905. doi: 10.1172/JCI115965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leying H., Suerbaum S., Kroll H. P., Stahl D., Opferkuch W. The capsular polysaccharide is a major determinant of serum resistance in K-1-positive blood culture isolates of Escherichia coli. Infect Immun. 1990 Jan;58(1):222–227. doi: 10.1128/iai.58.1.222-227.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medearis D. N., Jr, Camitta B. M., Heath E. C. Cell wall composition and virulence in Escherichia coli. J Exp Med. 1968 Sep 1;128(3):399–414. doi: 10.1084/jem.128.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Natanson C., Hoffman W. D., Suffredini A. F., Eichacker P. Q., Danner R. L. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med. 1994 May 1;120(9):771–783. doi: 10.7326/0003-4819-120-9-199405010-00009. [DOI] [PubMed] [Google Scholar]
- Norden C. W., Green G. M., Kass E. H. Antibacterial mechanisms of the urinary bladder. J Clin Invest. 1968 Dec;47(12):2689–2700. doi: 10.1172/JCI105952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Hanley P., Lalonde G., Ji G. Alpha-hemolysin contributes to the pathogenicity of piliated digalactoside-binding Escherichia coli in the kidney: efficacy of an alpha-hemolysin vaccine in preventing renal injury in the BALB/c mouse model of pyelonephritis. Infect Immun. 1991 Mar;59(3):1153–1161. doi: 10.1128/iai.59.3.1153-1161.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Hanley P., Low D., Romero I., Lark D., Vosti K., Falkow S., Schoolnik G. Gal-Gal binding and hemolysin phenotypes and genotypes associated with uropathogenic Escherichia coli. N Engl J Med. 1985 Aug 15;313(7):414–420. doi: 10.1056/NEJM198508153130704. [DOI] [PubMed] [Google Scholar]
- Orskov F. Agarose electrophoresis combined with second dimensional Cetavlon precipitation. A new method for demonstration of acidic polysaccharide K antigens. Acta Pathol Microbiol Scand B. 1976 Oct;84B(5):319–320. [PubMed] [Google Scholar]
- Orskov I., Orskov F. Escherichia coli in extra-intestinal infections. J Hyg (Lond) 1985 Dec;95(3):551–575. doi: 10.1017/s0022172400060678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pelkonen S., Häyrinen J., Finne J. Polyacrylamide gel electrophoresis of the capsular polysaccharides of Escherichia coli K1 and other bacteria. J Bacteriol. 1988 Jun;170(6):2646–2653. doi: 10.1128/jb.170.6.2646-2653.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pluschke G., Mayden J., Achtman M., Levine R. P. Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing. Infect Immun. 1983 Dec;42(3):907–913. doi: 10.1128/iai.42.3.907-913.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porat R., Johns M. A., McCabe W. R. Selective pressures and lipopolysaccharide subunits as determinants of resistance of clinical isolates of gram-negative bacilli to human serum. Infect Immun. 1987 Feb;55(2):320–328. doi: 10.1128/iai.55.2.320-328.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Russo T. A., Guenther J. E., Wenderoth S., Frank M. M. Generation of isogenic K54 capsule-deficient Escherichia coli strains through TnphoA-mediated gene disruption. Mol Microbiol. 1993 Jul;9(2):357–364. doi: 10.1111/j.1365-2958.1993.tb01696.x. [DOI] [PubMed] [Google Scholar]
- Russo T. A., Liang Y., Cross A. S. The presence of K54 capsular polysaccharide increases the pathogenicity of Escherichia coli in vivo. J Infect Dis. 1994 Jan;169(1):112–118. doi: 10.1093/infdis/169.1.112. [DOI] [PubMed] [Google Scholar]
- Russo T. A., Moffitt M. C., Hammer C. H., Frank M. M. TnphoA-mediated disruption of K54 capsular polysaccharide genes in Escherichia coli confers serum sensitivity. Infect Immun. 1993 Aug;61(8):3578–3582. doi: 10.1128/iai.61.8.3578-3582.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Russo T. A., Sharma G., Brown C. R., Campagnari A. A. Loss of the O4 antigen moiety from the lipopolysaccharide of an extraintestinal isolate of Escherichia coli has only minor effects on serum sensitivity and virulence in vivo. Infect Immun. 1995 Apr;63(4):1263–1269. doi: 10.1128/iai.63.4.1263-1269.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandberg T., Kaijser B., Lidin-Janson G., Lincoln K., Orskov F., Orskov I., Stokland E., Svanborg-Edén C. Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection. J Clin Microbiol. 1988 Aug;26(8):1471–1476. doi: 10.1128/jcm.26.8.1471-1476.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith H. W., Huggins M. B. The association of the O18, K1 and H7 antigens and the Co1V plasmid of a strain of Escherichia coli with its virulence and immunogenicity. J Gen Microbiol. 1980 Dec;121(2):387–400. doi: 10.1099/00221287-121-2-387. [DOI] [PubMed] [Google Scholar]
- Stamm W. E., Counts G. W., Running K. R., Fihn S., Turck M., Holmes K. K. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med. 1982 Aug 19;307(8):463–468. doi: 10.1056/NEJM198208193070802. [DOI] [PubMed] [Google Scholar]
- Stendahl O., Normann B., Edebo L. Influence of O and K antigens on the surface properties of Escherichia coli in relation to phagocytosis. Acta Pathol Microbiol Scand B. 1979 Apr;87B(2):85–91. doi: 10.1111/j.1699-0463.1979.tb02408.x. [DOI] [PubMed] [Google Scholar]
- Suzuki Y., Fukushi Y., Orikasa S., Kumagai K. Opsonic effect of normal and infected human urine on phagocytosis of Escherichia coli and yeasts by neutrophils. J Urol. 1982 Feb;127(2):356–360. doi: 10.1016/s0022-5347(17)53781-7. [DOI] [PubMed] [Google Scholar]
- Svanborg-Edén C., Hagberg L., Hull R., Hull S., Magnusson K. E., Ohman L. Bacterial virulence versus host resistance in the urinary tracts of mice. Infect Immun. 1987 May;55(5):1224–1232. doi: 10.1128/iai.55.5.1224-1232.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor P. W. Bactericidal and bacteriolytic activity of serum against gram-negative bacteria. Microbiol Rev. 1983 Mar;47(1):46–83. doi: 10.1128/mr.47.1.46-83.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor P. W., Koutsaimanis K. G. Experimental Escherichia coli urinary infection in the rat. Kidney Int. 1975 Oct;8(4):233–238. doi: 10.1038/ki.1975.106. [DOI] [PubMed] [Google Scholar]
- Timmis K. N., Boulnois G. J., Bitter-Suermann D., Cabello F. C. Surface components of Escherichia coli that mediate resistance to the bactericidal activities of serum and phagocytes. Curr Top Microbiol Immunol. 1985;118:197–218. doi: 10.1007/978-3-642-70586-1_11. [DOI] [PubMed] [Google Scholar]
- Tsai C. M., Frasch C. E. A sensitive silver stain for detecting lipopolysaccharides in polyacrylamide gels. Anal Biochem. 1982 Jan 1;119(1):115–119. doi: 10.1016/0003-2697(82)90673-x. [DOI] [PubMed] [Google Scholar]
- Verweij-van Vught A. M., van den Bosch J. F., Namavar F., Sparrius M., MacLaren D. M. K antigens of Escherichia coli and virulence in urinary-tract infection: studies in a mouse model. J Med Microbiol. 1983 May;16(2):147–155. doi: 10.1099/00222615-16-2-147. [DOI] [PubMed] [Google Scholar]
- Vosti K. L., Randall E. Sensitivity of serologically classified strains of escherichia coli of human origin to the serum bactericidal system. Am J Med Sci. 1970 Feb;259(2):114–119. doi: 10.1097/00000441-197002000-00005. [DOI] [PubMed] [Google Scholar]
- van den Bosch J. F., Postma P., Koopman P. A., de Graaff J., MacLaren D. M., van Brenk D. G., Guinée P. A. Virulence of urinary and faecal Escherichia coli in relation to serotype, haemolysis and haemagglutination. J Hyg (Lond) 1982 Jun;88(3):567–577. doi: 10.1017/s002217240007042x. [DOI] [PMC free article] [PubMed] [Google Scholar]