Roles of lytic transglycosylases in biofilm formation and β-lactam resistance in methicillin-resistant .

is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in remains largely unknown. The only known LTs in are immunodominant staphylococcal antigen A (IsaA) and D protein (SceD). Our study demonstrates that, in a strain of methicillin-resistant (MRSA), IsaA and SceD contribute differently to biofilm formation and β-lactam resistance. Deletion of , but not , led to decreased biofilm formation. Additionally, in -deleted strains, β-lactam resistance was significantly decreased compared to that of wild-type strains. Plasmid-based expression of , a major determinant of β-lactam resistance in MRSA, in an -deleted strain did not restore β-lactam resistance, demonstrating that the β-lactam susceptibility phenotype is exhibited by mutant regardless of the production level of PBP2a. Overall, our results suggest that IsaA is a potential therapeutic target for MRSA infections.