Exploring naphthoquinone and anthraquinone derivatives as antibiotic adjuvants against Staphylococcus aureus biofilms: Synergistic effects of menadione

Microb Pathog. 2024 Oct:195:106886. doi: 10.1016/j.micpath.2024.106886. Epub 2024 Aug 31.

Abstract

Given the ability of Staphylococcus aureus to form biofilms and produce persister cells, making infections difficult to treat with antibiotics alone, there is a pressing need for an effective antibiotic adjuvant to address this public health threat. In this study, a series of quinone derivatives were evaluated for their antimicrobial and antibiofilm activities against methicillin-susceptible and methicillin-resistant S. aureus reference strains. Following analyses using broth microdilution, growth curve analysis, checkerboard assay, time-kill experiments, and confocal laser scanning microscopy, menadione was identified as a hit compound. Menadione exhibited a notable antibacterial profile (minimum inhibitory concentration, MIC = 4-16 μg/ml; minimum bactericidal concentration, MBC = 256 μg/ml) against planktonic S. aureus and its biofilms (minimum biofilm inhibitory concentration, MBIC50 = 0.0625-0.25 μg/ml). When combined with oxacillin, erythromycin, and vancomycin, menadione exhibited a synergistic or additive effect against planktonic cells and biofilms of two S. aureus reference strains and six clinical isolates, highlighting its potential as a suitable adjuvant for further development against S. aureus biofilm-associated infections.

Keywords: Antibiofilm activity; Antibiotic adjuvant; Antimicrobial agents; MRSA; Naphthoquinone.

MeSH terms

  • Anthraquinones / pharmacology
  • Anti-Bacterial Agents* / pharmacology
  • Biofilms* / drug effects
  • Biofilms* / growth & development
  • Drug Synergism*
  • Erythromycin / pharmacology
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests*
  • Naphthoquinones* / pharmacology
  • Oxacillin / pharmacology
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus* / drug effects
  • Vancomycin / pharmacology
  • Vitamin K 3* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Vitamin K 3
  • Naphthoquinones
  • Oxacillin
  • Anthraquinones
  • Erythromycin
  • Vancomycin