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Microbiology 155 (2009), 1093-1102; DOI  10.1099/mic.0.024802-0
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Microbiology 155 (2009), 1093-1102; DOI  10.1099/mic.0.024802-0
© 2009 Society for General Microbiology

Global transcriptional response to vancomycin in Mycobacterium tuberculosis

Roberta Provvedi1, Francesca Boldrin2, Francesco Falciani3, Giorgio Palù2 and Riccardo Manganelli2

1 Department of Biology, University of Padua, 35100 Padua, Italy
2 Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35100 Padua, Italy
3 School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

Correspondence
Riccardo Manganelli
riccardo.manganelli{at}unipd.it

In order to gain additional understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify potential targets for new antibacterial drugs, we analysed the variation of the Mycobacterium tuberculosis transcriptional profile in response to inhibitory and subinhibitory concentrations of vancomycin. Our analysis identified 153 genes differentially regulated after exposing bacteria to a concentration of the drug ten times higher than the MIC, and 141 genes differentially expressed when bacteria were growing in a concentration of the drug eightfold lower than the MIC. Hierarchical clustering analysis indicated that the response to these different conditions is different, although with some overlap. This approach allowed us to identify several genes whose products could be involved in the protection from antibiotic stress targeting the envelope and help to confer the basal level of M. tuberculosis resistance to antibacterial drugs, such as Rv2623 (UspA-like), Rv0116c, PE20-PPE31, PspA and proteins related to toxin–antitoxin systems. Moreover, we also demonstrated that the alternative sigma factor {sigma}E confers basal resistance to vancomycin, once again underlining its importance in the physiology of the mycobacterial surface stress response.

Abbreviations: HCL, hierarchical clustering; SAM, significance analysis of microarrays

The data discussed in this publication have been deposited in the NCBI Gene Expression Omnibus under GEO Series accession number GSE12364.

Five supplementary tables are available with the online version of this paper.




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