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

Abstract

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.

Keywords: Biofilms; Clp protease; Modulators; Persisters; Resistance; Staphylococcus aureus; Toxin-antitoxin system; Virulence; agr signaling.