Chemical Intervention on Staphylococcus aureus Virulence

Abstract

Resistance to conventional antibiotics has raised worldwide attention. Notably, Methicillin‐resistant Staphylococcus aureus (MRSA) has become one of the most life‐threatening health concerns. Although effective against bacterial infections, conventional antibiotics have also showed a series of side effects such as gut microbiota imbalance. An alternative is in urgent need in order to combat bacterial infections. Antivirulence represents a new approach to circumvent these shortcomings, which focuses on disarming the “weapons” for pathogenicity without much selective pressure on bacterial survival. In this review, we place emphasis on the chemical modulation of biosynthesis, assembly, function and the regulation of some major virulence factors in S. aureus, which we hope will help the development of antivirulence modulators.

Synthesis and Structure‐Activity Relationships of Ring‐Opened Bengamide Analogues against Methicillin‐ResistantStaphylococcus aureus†

“…[ 6 ] Given the rigorous situation of MRSA, the search for new antibiotic molecules (especially for new chemical structures and novel mechanisms of action) is an urgent need. [ 7 ]…”

Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella

“…5 Sortase A (SrtA), a membrane-associated cysteine transpeptidase, is essential for bacterial pathogenesis but not for bacterial growth and survival. [8][9][10][11][12][13][14] The housekeeping SrtA specifically recognizes the conserved LPXTG motif of surface proteins and anchors them to the cell wall peptidoglycan. 9 Some surface proteins in the cell envelope are essential for adherence of pathogenic bacteria to host tissues and thus for establishing infections.…”

Tideglusib and Its Analogues As Inhibitors of Staphylococcus aureus SrtA

“…However, the inappropriate use and abuse of antibiotics have led to the emergence of drug-resistant bacteria, such as methicillin-resistant S. aureus (MRSA), which is the most common cause of the nosocomial infections and is difficult to treat due to resistance against many different drugs. − In order to alleviate antimicrobial resistance, the continued research for new antibiotics is necessary. In addition, antibacterial drug discovery should highlight the needs for new anti-infective agents, particularly those with new modes of action, such as antivirulence compounds. − …”