Loss of regulatory protein RfaH attenuates virulence of uropathogenic Escherichia coli.
RfaH is a regulatory protein in Escherichia coli and Salmonella enterica serovar Typhimurium. Although it enhances expression of different factors that are proposed to play a role in bacterial virulence, a direct effect of RfaH on virulence has not been investigated so far. We report that inactivation of rfaH dramatically decreases the virulence of uropathogenic E. coli strain 536 in an ascending mouse model of urinary tract infection. The mortality rate caused by the wild-type strain in this assay is 100%, whereas that of its isogenic rfaH mutant does not exceed 18%. In the case of coinfection, the wild-type strain 536 shows higher potential to colonize the urinary tract even when it is outnumbered 100-fold by its rfaH mutant in the inoculum. In contrast to the wild-type strain, serum resistance of strain 536rfaH::cat is fully abolished. Furthermore, we give evidence that, besides a major decrease in the amount of hemin receptor ChuA (G. Nagy, U. Dobrindt, M. Kupfer, L. Emody, H. Karch, and J. Hacker, Infect. Immun. 69:1924-1928, 2001), loss of the RfaH protein results in an altered lipopolysaccharide phenotype as well as decreased expression of K15 capsule and alpha-hemolysin, whereas levels of other pathogenicity factors such as siderophores, flagella, Prf, and S fimbriae appear to be unaltered in strain 536rfaH::cat in comparison to the wild-type strain. trans complementation of the mutant strain with the rfaH gene restores wild-type levels of the affected virulence factors and consequently restitutes virulence in the mouse model of ascending urinary tract infection.
Institute of Medical Microbiology and Immunology, University of Pécs, Hungary.
Gábor
G
Nagy
Ulrich
U
Dobrindt
György
G
Schneider
A Salam
AS
Khan
Jörg
J
Hacker
Levente
L
Emödy
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D010445:Peptide Elongation Factors / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014774:Virulence
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D010445:Peptide Elongation Factors; C106401:RfaH protein, E coli; D015534:Trans-Activators