Significance of the d -Serine-Deaminase and d -Serine Metabolism of Staphylococcus saprophyticus for Virulence

Abstract

ABSTRACT Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a d -serine-deaminase (DsdA). As d -serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the d -serine-deaminase gene is found in the genome of uropathogens. It has been suggested that d -serine-deaminase or the ability to respond to or to metabolize d -serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular d -serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high d -serine concentrations; however, its d -serine metabolism has not been described. The activity of the d -serine-deaminase was verified by analyzing the formation of pyruvate from d -serine in different strains with and without d -serine-deaminase. Cocultivation experiments were performed to show that d -serine-deaminase confers a growth advantage to S. saprophyticus in the presence of d -serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the Δ dsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of d -serine. In addition, we show that S. saprophyticus is able to use d -serine as the sole carbon source, but interestingly, d -serine had a negative effect on growth when glucose was also present. Taken together, d -serine metabolism is associated with virulence in S. saprophyticus , as at least one known virulence factor is upregulated in the presence of d -serine and a Δ dsdA mutant was attenuated in virulence murine model of urinary tract infection.