Deciphering the impact of on human health, and exploration of natural compounds as efflux pump inhibitors to treat multidrug resistance.

Kumarappan Chidambaram, Karthiga Sivarajan, Ramya Ravindhiran, Jothi Nayaki Sekar, Rajeswari Murugesan, Kavitha Dhandapani

Journal: Journal of medical microbiology 2024;73(8):

PMID: 39212030

Abstract

is an ESKAPE pathogen and threatens human health by generating infections with high fatality rates. leads to a spectrum of infections such as skin and wound infections, endocarditis, meningitis pneumonia, septicaemia and urinary tract infections. Recently, strains of have emerged as multidrug-resistant (MDR), meaning they are resistant to at least three different classes of antibiotics. MDR development is primarily intensified by widespread antibiotic misuse and inadequate stewardship. The World Health Organization (WHO) declared a precarious MDR species. maintains the MDR phenotype via a diverse array of antimicrobial metabolite-hydrolysing enzymes, efflux of antibiotics, impermeability and antibiotic target modification, thereby complicating treatment. Hence, a deeper understanding of the resistance mechanisms employed by MDR can give possible approaches to treat antimicrobial resistance. Resistance-nodulation-cell division (RND) efflux pumps have been identified as the key contributors to MDR determinants, owing to their capacity to force a broad spectrum of chemical substances out of the bacterial cell. Though synthetic inhibitors have been reported previously, their efficacy and safety are of debate. As resistance-modifying agents, phytochemicals are ideal choices. These natural compounds could eliminate the bacteria or interact with pathogenicity events and reduce the bacteria's ability to evolve resistance. This review aims to highlight the mechanism behind the multidrug resistance in and elucidate the utility of natural compounds as efflux pump inhibitors to deal with the infections caused by .

Address: Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore 641043, Tamil Nadu, India.; Department of Pharmacology and Toxicology, School of Pharmacy, King Khalid University, Abha 652529, Saudi Arabia.

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