Journal article
Mutations upstream of fabI in triclosan resistant Staphylococcus aureus strains are associated with elevated fabI gene expression
BMC Genomics, Vol.16, Article number: 345
2015
Abstract
Background
The enoyl-acyl carrier protein (ACP) reductase enzyme (FabI) is the target for a series of antimicrobial agents including novel compounds in clinical trial and the biocide triclosan. Mutations in fabI and heterodiploidy for fabI have been shown to confer resistance in S. aureus strains in a previous study. Here we further determined the fabI upstream sequence of a selection of these strains and the gene expression levels in strains with promoter region mutations.
Results
Mutations in the fabI promoter were found in 18% of triclosan resistant clinical isolates, regardless the previously identified molecular mechanism conferring resistance. Although not significant, a higher rate of promoter mutations were found in strains without previously described mechanisms of resistance. Some of the mutations identified in the clinical isolates were also detected in a series of laboratory mutants. Microarray analysis of selected laboratory mutants with fabI promoter region mutations, grown in the absence of triclosan, revealed increased fabI expression in three out of four tested strains. In two of these strains, only few genes other than fabI were upregulated. Consistently with these data, whole genome sequencing of in vitro selected mutants identified only few mutations except the upstream and coding regions of fabI, with the promoter mutation as the most probable cause of fabI overexpression. Importantly the gene expression profiling of clinical isolates containing similar mutations in the fabI promoter also showed, when compared to unrelated non-mutated isolates, a significant up-regulation of fabI.
Conclusions
In conclusion, we have demonstrated the presence of C34T, T109G, and A101C mutations in the fabI promoter region of strains with fabI up-regulation, both in clinical isolates and/or laboratory mutants. These data provide further observations linking mutations upstream fabI with up-regulated expression of the fabI gene.
Details
- Title
- Mutations upstream of fabI in triclosan resistant Staphylococcus aureus strains are associated with elevated fabI gene expression
- Authors/Creators
- D. Grandgirard (Author/Creator) - University of BernL. Furi (Author/Creator) - University of SienaM.L. Ciusa (Author/Creator) - University of SienaL. Baldassarri (Author/Creator) - Istituto Superiore di SanitàD.R. Knight (Author/Creator) - The University of Western AustraliaI. Morrissey (Author/Creator) - Quotient Clinical (United Kingdom)C.R. Largiadèr (Author/Creator) - University Hospital of BernS.L. Leib (Author/Creator) - Spiez LaboratoryM.R. Oggioni (Author/Creator) - University of Siena
- Publication Details
- BMC Genomics, Vol.16, Article number: 345
- Publisher
- Biomed Central
- Identifiers
- 991005541352507891
- Copyright
- © 2015 Grandgirard et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- 3.198 Mycotoxins
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