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Published on: July 7, 2020
Recent advances in Clp protease modulation to address virulence, resistance and persistence of MRSA infection
Yuan Ju1, Qi An2, Yiwen Zhang3
1Center of Infectious Diseases and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Sichuan University Library, Sichuan University, Chengdu 610041, China.
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.
Insights
The Clp protease regulates virulence and persistence in Staphylococcus aureus (MRSA) by degrading proteins. This review explores Clp protease
Area of Science:
- Microbiology and Molecular Biology: Focuses on bacterial protein degradation and virulence mechanisms.
Background:
- The Clp protease plays a critical role in Staphylococcus aureus (S. aureus) pathogenesis.
- It is involved in protein quality control, virulence factor production, biofilm formation, and persistence.
Purpose of the Study:
- To review recent advancements in understanding the Clp protease's role in S. aureus virulence and persistence.
- To highlight the Clp protease's involvement in methicillin-resistant S. aureus (MRSA) resistance mechanisms.
- To provide an overview of Clp modulators for treating MRSA infections.
Main Methods:
- Literature review of recent studies on Clp protease function in S. aureus.
- Analysis of research on virulence regulation, biofilm, and persister cell formation.
- Examination of studies on toxin-antitoxin systems and Clp protease interactions.
- Overview of therapeutic strategies targeting Clp protease.
Main Results:
- Clp protease controls S. aureus virulence through agr signaling.
- It degrades antitoxins in toxin-antitoxin systems, modulating persister and biofilm formation.
- Clp protease is implicated in MRSA resistance mechanisms.
Conclusions:
- Clp protease is a key regulator of virulence and persistence in S. aureus.
- Targeting Clp protease offers a potential strategy for combating MRSA infections.
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