Recent advances in Clp protease modulation to address virulence, resistance and persistence of MRSA infection.

The Clp protease is an AAA protease that executes abnormally folded or malfunctioning proteins, and has an important role in producing virulence factors, forming biofilms or persisters and developing methicillin-resistant Staphylococcus aureus (MRSA). Recent studies showed that Clp protease controls virulence via agr signaling and degrades antitoxins of the toxin-antitoxin system to modulate the formation of persisters and biofilms. In this review, we focus on recent developments concerning the virulence and persistence regulatory pathways and resistance-related mechanism of Clp protease in S. aureus, with an overview of the Clp modulators developed to treat MRSA infection.