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D-Serine Can Modify the Wall Teichoic Acid of MRSA via the dlt Pathway
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D-Serine Can Modify the Wall Teichoic Acid of MRSA via the dlt Pathway
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D-Serine Can Modify the Wall Teichoic Acid of MRSA via the dlt Pathway
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Journal Article
D-Serine Can Modify the Wall Teichoic Acid of MRSA via the dlt Pathway
2025
Overview
Methicillin-resistant Staphylococcus aureus (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 dlt 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 dlt 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 S. aureus 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 dlt pathway, and its possible involvement in D-Ser sensitization deserves further investigation.
Publisher
MDPI AG,MDPI
Subject
/ Analysis
/ Animals
/ Anti-Bacterial Agents - pharmacology
/ Bacteria
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Biofilms
/ Enzymes
/ Genes
/ Methicillin-Resistant Staphylococcus aureus - drug effects
/ Methicillin-Resistant Staphylococcus aureus - genetics
/ Methicillin-Resistant Staphylococcus aureus - metabolism
/ Methicillin-Resistant Staphylococcus aureus - pathogenicity
/ Mice
/ Operon
/ Peptides
/ Serine
/ Staphylococcal Infections - drug therapy
/ Staphylococcal Infections - microbiology
