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Infect. Immun. doi:10.1128/IAI.00652-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Roles of Serine Accumulation and Catabolism in the Colonization of the Murine Urinary Tract by Escherichia coli CFT073

Andrew T. Anfora, Brian J. Haugen, Paula Roesch, Peter Redford, and Rodney A. Welch*

Department of Medical Microbiology & Immunology, University of Wisconsin-Madison 1300 University Ave., Madison, WI 53706 USA

* To whom correspondence should be addressed. Email: rawelch{at}wisc.edu.


   Abstract

A D-serine deaminase (DsdA) mutant of uropathogenic Escherichia coli strain CFT073 has a hypercolonization phenotype in a murine model of urinary tract infection (UTI) due to increased virulence gene expression by an unknown mechanism (Haugen et al 2007. Infect Immun 75:278-289). DsdC is a D-serine-dependent activator of dsdXA transcription. DsdC may regulate the virulence genes responsible for hypercolonization. The loss of DsdA leads to increased intracellular accumulation of D-serine. In this study we show that deletion of the genes encoding L-serine deaminases, SdaA and SdaB resulted in a mutant that accumulates higher intracellular levels of L-serine than CFT073. CFT073 sdaA sdaB has a mild competitive colonization defect whereas a CFT073 dsdA sdaA sdaB triple mutant shows a greater loss in competitive colonization ability. Thus, the inability to generate serine-specific catabolic products does not result in hypercolonization and the ability to catabolize serine represents a positive physiological trait during murine UTI. CFT073 dsdC and CFT073 dsdC dsdA mutants continue to outcompete the wild type in the UTI model. These results confirm that loss of DsdA activity results in the hypercolonization phenotype and that DsdC does not play a direct role in the elevated colonization phenotype. Interestingly, a CFT073 dsdA mutant deleted for D-serine transporter genes, dsdX and cycA, shows wild type colonization levels of the bladder, but is attenuated for kidney colonization. Thus, D-serine acts as a signal for hypercolonization and virulence gene expression by CFT073 dsdA, whereas overall catabolism of serine represents a positive E. coli fitness trait during UTI.







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