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Diclofenac and Meloxicam Exhibited Anti-Virulence Activities Targeting Staphyloxanthin Production in

Rana A Elmesseri1, Sarra E Saleh2, Sarah A Ghobish3

  • 1Department of Microbiology, Faculty of Pharmacy, Misr International University (MIU), Cairo 19648, Egypt.

Antibiotics (Basel, Switzerland)
|February 25, 2023
PubMed

Insights

Meloxicam (MXM) and diclofenac (DC) effectively inhibit Staphylococcus aureus virulence by reducing staphyloxanthin (STX) production and downregulating key genes. These drugs show potential as novel anti-virulence agents against MRSA infections.

Area of Science:

  • Microbiology and Infectious Diseases
  • Pharmacology and Drug Discovery
  • Molecular Biology

Background:

  • Staphylococcus aureus (S. aureus) is a major global pathogen causing severe infections, with rising antimicrobial resistance necessitating new therapeutic strategies.
  • Methicillin-resistant S. aureus (MRSA) poses a significant threat in both hospital and community settings, highlighting the need for novel anti-pathogenic agents.
  • Staphyloxanthin (STX), a key virulence factor, is crucial for MRSA survival against host immune responses.

Purpose of the Study:

  • To evaluate the anti-virulence properties of meloxicam (MXM) and diclofenac (DC) against S. aureus, focusing on their impact on STX production.
  • To compare the efficacy of MXM and DC in inhibiting STX synthesis and downregulating virulence gene expression.
  • To investigate the potential of repurposing MXM and DC as adjuvants in combating MRSA infections.

Main Methods:

  • Qualitative and quantitative assessment of STX inhibition by DC and MXM in 80 S. aureus clinical isolates.
  • Quantitative gene expression analysis of STX biosynthetic genes (crtM, crtN, sigB) and the alpha-hemolysin gene (hla) with and without DC/MXM treatment.
  • Molecular docking analysis to confirm drug-target interactions.

Main Results:

  • DC and MXM demonstrated potent inhibition of STX synthesis, with inhibition rates of 79.3-98% and 80.6-96.7%, respectively.
  • Significant downregulation of STX biosynthetic genes (crtM, crtN, sigB) and the virulence gene hla was observed in treated S. aureus cells.
  • Computational studies confirmed strong binding interactions between DC/MXM and the CrtM binding site.

Conclusions:

  • Meloxicam and diclofenac exhibit significant anti-virulence activity against Staphylococcus aureus by inhibiting staphyloxanthin production.
  • These non-steroidal anti-inflammatory drugs effectively downregulate key virulence factors, offering a potential strategy to combat MRSA.
  • DC and MXM show promise for repurposing as adjuvant therapies alongside conventional antimicrobials to manage MRSA infections.
Keywords:
MRSAanti-virulencediclofenacmeloxicamsaphyloxanthin

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