Progress in the Prevalence, Classification and Drug Resistance Mechanisms of Methicillin-Resistant Staphylococcus aureus

Abstract

Staphylococcus aureus is a common human pathogen with a variety of virulence factors, which can cause multiple infectious diseases. In recent decades, due to the constant evolution and the abuse of antibiotics, Staphylococcus aureus was becoming more resistant, the infection rate of MRSA remained high, and clinical treatment of MRSA became more difficult. The genetic diversity of MRSA was mainly represented by the continuous emergence of epidemic strains, resulting in the constant changes of epidemic clones. Different classes of MRSA resulted in different epidemics and resistance characteristics, which could affect the clinical symptoms and treatments. MRSA had also spread from traditional hospitals to community and livestock environments, and the new clones established a relationship between animals and humans, promoting further evolution of MRSA. Since the resistance mechanism of MRSA is very complex, it is important to clarify these resistance mechanisms at the molecular level for the treatment of infectious diseases. We firstly described the diversity of SCCmec elements, and discussed the types of SCCmec, its drug resistance mechanisms and expression regulations. Then, we described how the vanA operon makes Staphylococcus aureus resistant to vancomycin and its expression regulation. Finally, a brief introduction was given to the drug resistance mechanisms of biofilms and efflux pump systems. Analyzing the resistance mechanism of MRSA can help study new anti-infective drugs and alleviate the evolution of MRSA. At the end of the review, we summarized the treatment strategies for MRSA infection, including antibiotics, anti-biofilm agents and efflux pump inhibitors. To sum up, here we reviewed the epidemic characteristics of Staphylococcus aureus, summarized its classifications, drug resistance mechanisms of MRSA (SCCmec element, vanA operon, biofilm and active efflux pump system) and novel therapy strategies, so as to provide a theoretical basis for the treatment of MRSA infection.

Keywords:

• biofilm
• efflux pump
• MRSA
• prevalence
• resistance mechanism
• SCCmec

Abbreviations

ABC, ATP-binding cassette superfamily; BORSA, borderline oxacillin-resistant Staphylococcus aureus; CA-MRSA, community-associated methicillin-resistant Staphylococcus aureus; ccr, cassette chromosome recombinase; eDNA, extracellular DNA; EPIs, efflux pump inhibitors; HA-MRSA, healthcare-associated methicillin-resistant Staphylococcus aureus; LA-MRSA, livestock-associated methicillin-resistant Staphylococcus aureus; MATE, multidrug and toxin extrusion family; MFS, major facilitator superfamily; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; orfX, open reading frame X; OS-MRSA, oxacillin-susceptible methicillin-resistant Staphylococcus aureus; RND, resistance nodulation division superfamily; S. aureus, Staphylococcus aureus; SCC, staphylococcal cassette chromosome; SMR, small multidrug resistance family; VRSA, vancomycin resistant Staphylococcus aureus.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This study was supported by Fundamental Research Program of Shanxi Province (Grant no. 20210302123397; 202203021212351), Key R&D Projects of Introducing High-Level Scientific and Technological Talents in Lvliang City (Grant no. 2021RC-1-4), the Project of Lvliang City Science and Technology Program (Grant no. 2020SHFZ29), Science and Technology Innovation Project of Colleges and Universities in Shanxi Province (Grant no. 2020L0749), the National College Students’ Innovation and Entrepreneurship Training Program (Grant no. 20221569), the Key Projects of Innovation and Entrepreneurship Training for College Students in Shanxi Province (Grant no. 20221577), Projects of Innovation and Entrepreneurship Training Program for College Students of Fenyang College of Shanxi Medical University (Grant no. FDC202209; FDC202214; FDC202215), and Special Fund for Key Disciplines of Fenyang College of Shanxi Medical University (Grant no. 2022B14).