D-Serine Can Modify the Wall Teichoic Acid of MRSA via the Pathway.

Methicillin-resistant (MRSA) infection is a serious clinical threat, and D-Serine (D-Ser) showed significant sensitization effects on β-lactams against MRSA in our previous study. Quantitative PCR analysis found the elevated expression of the operon with D-Ser combination, which is responsible for wall teichoic acid (WTA) modification involving D-Alanine (D-Ala). This study aims to verify the effect of D-Ser on WTA modification through the pathway and explore the related effects on bacteria. The DltA and DltC were recombined, and enzyme kinetic evaluations with different D-amino acids were then conducted; it was found that D-Ser is the second-best substrate for DltA (just after D-Ala), no matter whether DltC is present or not. D-Ser treatment also lowered WTA generation as demonstrated by WTA phosphate quantification and native-PAGE electrophoresis, increased the susceptibility of to polymyxins, and elevated the mouse survival rate in the MRSA intraperitoneal infection model without affecting the bacterial loads in the main organs, indicating possible effects of D-Ser on MRSA virulence through WTA modification. In conclusion, the current study provided evidence for D-Ser modification of WTA via the pathway, and its possible involvement in D-Ser sensitization deserves further investigation.