Natural products acting against S. aureus through membrane and cell wall disruption

Abstract

Staphylococcus aureus (S. aureus) is responsible for several community and hospital-acquired infections with life-threatening complications such as bacteraemia, endocarditis, meningitis, liver abscess, and spinal cord epidural abscess. In recent decades, the abuse and misuse of antibiotics in humans, animals, plants, and fungi and the treatment of nonmicrobial diseases have led to the rapid emergence of multidrug-resistant pathogens. The bacterial wall is a complex structure consisting of the cell membrane, peptidoglycan cell wall, and various associated polymers. The enzymes involved in bacterial cell wall synthesis are established antibiotic targets and continue to be a central focus for antibiotic development. Natural products play a vital role in drug discovery and development. Importantly, natural products provide a starting point for active/lead compounds that sometimes need modification based on structural and biological properties to meet the drug criteria. Notably, microorganisms and plant metabolites have contributed as antibiotics for noninfectious diseases. In this study, we have summarized the recent advances in understanding the activity of the drugs or agents of natural origin that directly inhibit the bacterial membrane, membrane components, and membrane biosynthetic enzymes by targeting membrane-embedded proteins. We also discussed the unique aspects of the active mechanisms of established antibiotics or new agents.