A Nonclassical Mechanism of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus and Its Effect on Virulence
Nidhi Satishkumar, Li-Yin Lai, Nagaraja Mukkayyan, Bruce E. Vogel, Som S. Chatterjee
Abstract
Our study demonstrates the ability of PBP4 to be an important mediator of β-lactam resistance in not only methicillin-susceptible Staphylococcus aureus (MSSA) background strains as previously demonstrated but also in MRSA strains. When present together, PBP2a and PBP4 overexpression can produce increased levels of β-lactam resistance, causing complications in treatment. Thus, this study suggests the importance of monitoring PBP4-associated resistance in clinical settings, as well as understanding the mechanistic basis of associated resistance, so that treatments targeting PBP4 may be developed. This study also demonstrates that S. aureus strains with increased PBP4 expression are less pathogenic, providing important hints about the role of PBP4 in S. aureus resistance and pathogenesis.