Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

39Citations
Citations of this article
94Readers
Mendeley users who have this article in their library.

This article is free to access.

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 RSdid 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. © 2011 Riordan et al; licensee BioMed Central Ltd.

References Powered by Scopus

A new mathematical model for relative quantification in real-time RT–PCR

28527Citations
N/AReaders
Get full text

Significance analysis of microarrays applied to the ionizing radiation response

10035Citations
N/AReaders
Get full text

The crisis in antibiotic resistance

2495Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Adaptive and mutational resistance: Role of porins and efflux pumps in drug resistance

626Citations
N/AReaders
Get full text

In silico validation of the non-antibiotic drugs acetaminophen and ibuprofen as antibacterial agents against red complex pathogens

413Citations
N/AReaders
Get full text

Synergistic effect of non-steroidal anti-inflammatory drugs (NSAIDs) on antibacterial activity of cefuroxime and chloramphenicol against methicillin-resistant Staphylococcus aureus

89Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Riordan, J. T., Dupre, J. A. M., Cantore-Matyi, S. A., Kumar-Singh, A., Song, Y., Zaman, S., … Gustafson, J. E. (2011). Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac. Annals of Clinical Microbiology and Antimicrobials, 10. https://doi.org/10.1186/1476-0711-10-30

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 32

52%

Researcher 22

35%

Professor / Associate Prof. 8

13%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 24

44%

Medicine and Dentistry 13

24%

Biochemistry, Genetics and Molecular Bi... 10

19%

Immunology and Microbiology 7

13%

Save time finding and organizing research with Mendeley

Sign up for free