Mutations upstream of fabI in triclosan resistant Staphylococcus aureus strains are associated with elevated fabI gene expression

BMC Genomics

Marco R Oggioni⁸  Stephen L Leib⁴  Carlo R Largiadèr⁵  Ian Morrissey¹  Daniel R Knight⁷  Lucilla Baldassarri⁶  Maria Laura Ciusa³  Leonardo Furi³  Denis Grandgirard² 

[1] Current address: IHMA Europe Sa’rl, Epalinges, Switzerland;Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland;LA.M.M.B., Dip. Biotecnologie Mediche, Università di Siena, Siena, Italy;Biology Division, Spiez Laboratory, Federal Office for Civil Protection FOCP, Spiez, Switzerland;Institute of Clinical Chemistry, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland;Istituto Superiore di Sanità, Roma, Italy;Current address: The University of Western Australia, Nedlands, WA, Australia;Department of Genetics, University of Leicester, Leicester, UK

关键词: Promoter mutation;    Cross-resistance;    Microarray;    fabI;    Triclosan;    Resistance;    Biocide;   

Others  :  1177573
DOI  :  10.1186/s12864-015-1544-y

 received in 2014-05-01, accepted in 2015-04-17,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Grandgirard et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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