BACKGROUND: Capsule expression may be important during ascending Escherichia coli urinary tract infections (UTIs). METHODS: An isogenic ksl(k2)ABCDE mutant of extraintestinal pathogenic E. coli (ExPEC) strain CFT073 that could not synthesize the K2 capsule was compared with wild-type CFT073, to determine virulence in a murine model of ascending UTI and in vitro killing assays. RESULTS: No significant differences were observed regarding the abilities of the mutant and the wild-type CFT073 strains to colonize the murine urinary tract in single-challenge infection experiments. However, in competitive-colonization experiments, the mutant was significantly outcompeted by the wild-type strain in urine and the kidneys. The mutant strain was also more susceptible to human serum. Complementation of the mutant with a plasmid containing the ksl(k2)ABCDE genes restored capsule expression, enhanced survival in the murine urinary tract, and restored serum resistance. CONCLUSION: These results indicate that expression of the K2 capsule is important for the pathogenesis of UTI and provides protection against complement-mediated killing. To our knowledge, this is the first study in which the E. coli capsule has been proven to play a role in infection by use of isogenic mutants and genetic complementation.
BACKGROUND: Capsule expression may be important during ascending Escherichia coli urinary tract infections (UTIs). METHODS: An isogenic ksl(k2)ABCDE mutant of extraintestinal pathogenic E. coli (ExPEC) strain CFT073 that could not synthesize the K2 capsule was compared with wild-type CFT073, to determine virulence in a murine model of ascending UTI and in vitro killing assays. RESULTS: No significant differences were observed regarding the abilities of the mutant and the wild-type CFT073 strains to colonize the murine urinary tract in single-challenge infection experiments. However, in competitive-colonization experiments, the mutant was significantly outcompeted by the wild-type strain in urine and the kidneys. The mutant strain was also more susceptible to human serum. Complementation of the mutant with a plasmid containing the ksl(k2)ABCDE genes restored capsule expression, enhanced survival in the murine urinary tract, and restored serum resistance. CONCLUSION: These results indicate that expression of the K2 capsule is important for the pathogenesis of UTI and provides protection against complement-mediated killing. To our knowledge, this is the first study in which the E. coli capsule has been proven to play a role in infection by use of isogenic mutants and genetic complementation.
Authors: Elzbieta Brzuszkiewicz; Holger Brüggemann; Heiko Liesegang; Melanie Emmerth; Tobias Olschläger; Gábor Nagy; Kaj Albermann; Christian Wagner; Carmen Buchrieser; Levente Emody; Gerhard Gottschalk; Jörg Hacker; Ulrich Dobrindt Journal: Proc Natl Acad Sci U S A Date: 2006-08-15 Impact factor: 11.205
Authors: Eric L Buckles; Farah K Bahrani-Mougeot; Anita Molina; C Virgina Lockatell; David E Johnson; Cinthia B Drachenberg; Valerie Burland; Fred R Blattner; Michael S Donnenberg Journal: Infect Immun Date: 2004-07 Impact factor: 3.441
Authors: Meenu Mishra; Matthew S Byrd; Susan Sergeant; Abul K Azad; Matthew R Parsek; Linda McPhail; Larry S Schlesinger; Daniel J Wozniak Journal: Cell Microbiol Date: 2011-11-10 Impact factor: 3.715
Authors: Gregory G Anderson; Carlos C Goller; Sheryl Justice; Scott J Hultgren; Patrick C Seed Journal: Infect Immun Date: 2010-01-19 Impact factor: 3.441