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Thioridazine potentiates the effect of a beta-lactam antibiotic against Staphylococcus aureus independently of mecA

Marianne Ø Poulsen1, Kirstine Jacobsen, Mette Thorsing

  • 1Institute of Clinical Research, Research Unit of Clinical Microbiology, University of Southern Denmark, J.B. Winsløw Vej 21,2, DK-5000 Odense C, Denmark.

Research in Microbiology
|October 24, 2012
PubMed

Insights

The combination of thioridazine and dicloxacillin enhances killing effects against Staphylococcus aureus, including methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains. This synergistic effect is independent of the PBP2a resistance mechanism.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat.
  • Antimicrobial resistance necessitates novel therapeutic strategies.
  • Thioridazine, a neuroleptic, has shown potential in modulating bacterial susceptibility.

Purpose of the Study:

  • To investigate the combinatorial effect of thioridazine and dicloxacillin against a wide range of Staphylococcus aureus strains.
  • To analyze the impact of this combination on both MRSA and methicillin-susceptible S. aureus (MSSA).
  • To determine the role of the PBP2a resistance marker in the observed synergistic effect.

Main Methods:

  • Testing the combinatorial effect of thioridazine and dicloxacillin on clinical isolates of MRSA and MSSA.
  • Analyzing the transcription and translation of the mecA gene's resistance marker, PBP2a, using primer extension and western blotting.

Main Results:

  • Thioridazine increased dicloxacillin susceptibility in all tested MRSA isolates.
  • The synergistic effect was observed in MSSA strains, contrary to previous findings.
  • The combination potentiated the killing effect against a broad selection of clinical Staphylococcus aureus isolates.

Conclusions:

  • The combination of dicloxacillin and thioridazine demonstrates a potentiated killing effect against diverse Staphylococcus aureus strains.
  • This synergistic antimicrobial activity extends to both MRSA and MSSA.
  • The observed killing effect is independent of PBP2a-mediated resistance mechanisms.

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