Bacterial Targets of Antibiotics in Methicillin-Resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent bacterial pathogens and continues to be a leading cause of morbidity and mortality worldwide. MRSA is a commensal bacterium in humans and is transmitted in both community and healthcare settings. Successful treatment remains a challenge, and a search for new targets of antibiotics is required to ensure that MRSA infections can be effectively treated in the future. Most antibiotics in clinical use selectively target one or more biochemical processes essential for S. aureus viability, e.g., cell wall synthesis, protein synthesis (translation), DNA replication, RNA synthesis (transcription), or metabolic processes, such as folic acid synthesis. In this review, we briefly describe the mechanism of action of antibiotics from different classes and discuss insights into the well-established primary targets in S. aureus. Further, several components of bacterial cellular processes, such as teichoic acid, aminoacyl-tRNA synthetases, the lipid II cycle, auxiliary factors of β-lactam resistance, two-component systems, and the accessory gene regulator quorum sensing system, are discussed as promising targets for novel antibiotics. A greater molecular understanding of the bacterial targets of antibiotics has the potential to reveal novel therapeutic strategies or identify agents against antibiotic-resistant pathogens.

A novel bactericidal small molecule, STK-35, and its derivative, STK-66, as antibacterial agents against Gram-negative pathogenic bacteria in vitro and in vivo

“…These differences may be responsible for the different sensitivity of STK‐35/66 to different bacteria. And due to the unique structure of STK‐35/66, we speculated that these compounds may have mechanisms of action different from those of the existing antibiotics, including the inhibition of cell wall synthesis, transcription, translation, protein synthesis and folate metabolism (Lade and Kim 2021). Thus, after structure optimization of the core nucleus, STK‐35/66 have great potential as a new class of antimicrobial agents with broad antimicrobial spectra.…”

Antibacterial activity and chemical profile of the bioactive compounds from Aloe polyphylla Schönland

“…Computer-based molecular docking method was employed to understand the molecular interactions involved during the inhibition of bacterial growth based on the binding scores and types of bonds formed by the two most predominant GC-MS identi ed ligand and cipro oxacin with the receptor protein, penicillin-binding protein 2x (PDP2). PDP2 is a membrane-associated enzyme essential for cell growth as it is associated with peptidoglycan biosynthesis [29]. The three-dimensional structures of PDP2 were retrieved from Protein Data Bank (PDB ID: 1QMF).…”

Molecular Mechanisms Underlying the Inhibition of Proliferation and Differentiation by Florfenicol in P19 Stem Cells: Transcriptome Analysis

“…The bacterial ribosome becomes an important target of varieties of clinically useful antimicrobials ( Lade and Kim 2021 ). Mitochondria and chloroplasts have bacterial-type ribosomes because they are evolved from endosymbiotic α-proteobacteria and cyanobacteria-like prokaryotes, respectively ( Ferrari et al, 2021 ); this condition makes these organelles vulnerable to ribosome-targeted antimicrobials ( Wang et al, 2015 ).…”