Kunyu Shao,1,* Yuxun Yang,1,* Xuankai Gong,1,* Ke Chen,1,2 Zixiang Liao,1 Suvash Chandra Ojha2 

1School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Infectious Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Suvash Chandra Ojha, Email suvash_ojha@swmu.edu.cn

Abstract: The increasing incidence of antibiotic resistance in Staphylococcus aureus (S. aureus) poses a substantial threat to global public health. In recent decades, the evolution of bacteria and the misuse of antibiotics have led to a progressive development in drug resistance of S. aureus, resulting in a worldwide rise in methicillin-resistant S. aureus (MRSA) infection rates. Understanding the molecular mechanisms underlying staphylococcal drug resistance, the treatments for staphylococcal infections, and the efficacy of nanomaterials in addressing multi-drug resistance is crucial. This review explores the resistance mechanisms, which include limiting drug uptake, target modification, drug inactivation through the production of degrading enzymes, and active efflux of drugs. It also examines the current therapeutic strategies, such as antibiotic combination therapy, phage therapy, monoclonal antibody therapy, and nanoparticle therapy, with a particular emphasis on the role of silver-based nanomaterials. Nanoparticles possess the ability to overcome multi-drug resistance, offering a novel avenue for the management of drug-resistant bacteria. The nanomaterials have demonstrated potent antibacterial activity against S. aureus through various mechanisms, including cell membrane disruption, generation of reactive oxygen species (ROS), and inhibition of essential cellular processes. It also highlights the need for further research to optimize nanoparticle design, enhance their antibacterial potency, and ensure their biocompatibility and biodegradability. The review ultimately concludes by emphasizing the importance of a multifaceted approach to treatment, including the development of new antibiotics, investment in stewardship programs to prevent antibiotic misuse, and the exploration of natural compounds and bacteriocins as potential antimicrobial agents.

Keywords: Staphylococcus aureus, MRSA, drug resistance mechanism, antimicrobial therapy, nanomaterials’ antistaphylococcal mechanism