Nonsteroidal antiinflammatory drugs alter antibiotic susceptibility and expression of virulence-related genes and protein A of Staphylococcus aureus

Turk J Med Sci. 2021 Apr 30;51(2):835-847. doi: 10.3906/sag-2003-60.

Abstract

Background/aim: Nonsteroidal antiinflammatory drugs (NSAIDs) including diclofenac, naproxen, ibuprofen, acetylsalicylic acid, and acetaminophen have been shown to have antimicrobial effects on various microorganisms. The aim of this study was to investigate the antibacterial effects of NSAIDs on Staphylococcus aureus.

Materials and methods: Susceptibilities of S. aureus strains to NSAIDs with or without antimicrobials (moxifloxacin, vancomycin, ciprofloxacin, clindamycin, and gentamicin) were determined using the microdilution method and disk diffusion test. Expression levels of genes in the presence of drugs were investigated by real-time quantitative RT-PCR (qRT-PCR), and immunoblotting analysis was performed for staphylococcal protein A (SpA).

Results: Our results showed that all NSAIDs were active against S. aureus strains with MIC values ranging from 195 μg/mL to 6250 μg/ mL. NSAIDs increased the antibiotic susceptibility of the strains, and diclofenac was found to be more effective than the other drugs. Drugs showed different effects on expression levels of virulence factor and/or regulatory genes. Immunoblotting analysis of SpA protein was mostly in accordance with qRT-PCR results.

Conclusion: The regulatory/virulence factor genes and proteins of S. aureus investigated in this study may be reasonable targets for these drugs, and we suggest that the data may contribute to the field of infection control and antimicrobial resistance.

Keywords: Gene expression; Staphylococcus aureus; antibiotic sensitivity; immunoblotting; real-time qRT-PCR; nonsteroidal antiinflammatory drugs.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Diclofenac / pharmacology
  • Gene Expression / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Real-Time Polymerase Chain Reaction
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Protein A / genetics
  • Staphylococcal Protein A / therapeutic use
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Virulence / drug effects*
  • Virulence / genetics
  • Virulence Factors / genetics

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Staphylococcal Protein A
  • Virulence Factors
  • Diclofenac