Characterization of the response of uropathogenic Escherichia coli strain CFT073 to D-serine

Uropathogenic Escherichia coli are the primary cause of community-acquired urinary tract infections. Studies of the uropathogenic E. coli isolate CFT073 suggest that D-serine is a key signaling molecule. D-serine is the stereoisomer of the proteogenic amino acid L-serine, and is present in mammalian urine at levels ranging from 3.0 to 40 mug ml-1, making it one of the most abundant amino acids found in urine. During experimental urinary tract infection of mice, CFT073 dsdA, which lacks the gene coding for D-serine deaminase and is unable to degrade D-serine, colonizes the bladders and kidneys at increased numbers relative to wild type CFT073. Analysis of additional mutants suggests that this hypercolonization is dependent upon intracellular accumulation of host-derived D-serine. By comparing the global gene expression of wild type CFT073 and CFT073 dsdA, we found upregulation of a number of established virulence factors, as well as a number of known and predicted membrane associated proteins. We also found evidence for D-serine accumulation during infection, as the D-serine responsive genes dsdX and dsdA were also upregulated. We implicated the upregulated genes encoding hemolysin, P fimbriae, and additional unknown proteins as being necessary for hypercolonization by CFT073 dsdA by deleting them from CFT073 dsdA, then analyzing the colonization behaviors of these mutants. We speculate the upregulation of these genes is dependent upon D-serine accumulation and D-serine incorporation into peptidoglycan.