Alterations In the Transciptome and Antibiotic Susceptibility of Staphylococcus aureus Grown In the Presence of Diclofenac

Authors

James T. Riordan, University of South FloridaFollow
JoAnne M. Dupre, Nex Mexico State University
Stephanie A. Cantore-Matyi, New Mexico State University
Atul Kumar-Singh, Illinois State University
Yang Song, Illinois State University
Shahrear Zaman, New Mexico State UniversityFollow
Sonia Horan, New Mexico State University
Nada S. Helal, University of South Florida
Vijayaraj Nagarajan, University of Southern MississippiFollow
Mohamed O. Elasri, University of Southern MississippiFollow
Brian J. Wilkinson, Illinois State UniversityFollow
John E. Gustafson, New Mexico State UniversityFollow

Document Type

Article

Publication Date

7-21-2011

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

Background

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (Dc^RS) S. aureus strains.

Methods

Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry.

Results

Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σ^B), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σ^B-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to Dc^RS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation.

Conclusions

The results of this study suggest that diclofenac influences antibiotic susceptibility in S. aureus, in part, by altering the expression of regulatory and structural genes associated with cell wall biosynthesis/turnover and transport.

Comments

Published by Annals of Clinical Microbiology and Antimicrobials at 10.1186/1476-0711-10-30.

Publication Title

Annals of Clinical Microbiology and Antimicrobials

Volume

10

Issue

30

First Page

1

Last Page

11

Recommended Citation

Riordan, J. T., Dupre, J. M., Cantore-Matyi, S. A., Kumar-Singh, A., Song, Y., Zaman, S., Horan, S., Helal, N. S., Nagarajan, V., Elasri, M. O., Wilkinson, B. J., Gustafson, J. E. (2011). Alterations In the Transciptome and Antibiotic Susceptibility of Staphylococcus aureus Grown In the Presence of Diclofenac. Annals of Clinical Microbiology and Antimicrobials, 10(30), 1-11.
Available at: https://aquila.usm.edu/fac_pubs/15140