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Overexpression of eis without a mutation in promoter region of amikacin- and kanamycin-resistant Mycobacterium tuberculosis clinical strain
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Document Title
Overexpression of eis without a mutation in promoter region of amikacin- and kanamycin-resistant Mycobacterium tuberculosis clinical strain
Author
Sowajassatakul A., Prammananan T., Chaiprasert A., Phunpruch S.
Name from Authors Collection
Affiliations
King Mongkut's Institute of Technology Ladkrabang, Department of Biology, Faculty of Science, Bangkok, 10520, Thailand; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Tuberculosis Research Laboratory, Pathum Thani, 12120, Thailand; Mahidol University, Research Affairs, Faculty of Medicine Siriraj Hospital, Bangkok, 10700, Thailand; King Mongkut's Institute of Technology Ladkrabang, Bioenergy Research Unit, Faculty of Science, Bangkok, 10520, Thailand
Type
Article
Source Title
Annals of Clinical Microbiology and Antimicrobials
ISSN
14760711
Year
2018
Volume
17
Issue
1
Open Access
Gold, Green
Publisher
BioMed Central Ltd.
DOI
10.1186/s12941-018-0285-6
Abstract
Background: Aminoglycosides such as amikacin and kanamycin are effective injectable second-line drugs for treatment of multidrug-resistant tuberculosis. Molecular mechanisms underlying aminoglycoside resistance are not well understood. We have previously identified the amikacin- and kanamycin-resistant M. tuberculosis MT433 clinical strain, of which all known mutations related to resistance have not been found. Drug efflux pump is one of reported resistance mechanisms that might play a role in aminoglycoside resistance. Methods: The expression levels of sixteen putative efflux pump genes, including eis and one regulator gene, whiB7, of MT433 in the presence of kanamycin were determined using the reverse transcription-quantitative PCR method. The effects of upregulated genes on amikacin and kanamycin resistance were investigated by overexpression in M. tuberculosis H37Ra strain. Results: Upon kanamycin exposure, other than whiB7 and eis that were found extremely overexpressed, two drug efflux pump genes, namely Rv1877 and Rv2846c, showed specifically high-level of expression in M. tuberculosis MT433 strain. However, direct effect of overexpressed Rv1877 and Rv2846c on amikacin and kanamycin resistance could not be demonstrated in M. tuberculosis H37Ra overexpressed strain. Conclusions: Our finding demonstrated that overexpression of eis could occur without any mutations in the promoter region and be detectable in clinical isolate. This might be a consequence of overexpressed whiB7, resulting in amikacin and kanamycin resistance in M. tuberculosis MT433 strain. © 2018 The Author(s).
Keyword
Aminoglycoside | Drug resistance | Efflux pump | eis | Tuberculosis | whiB7
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
National Science and Technology Development Agency; King Mongkut's Institute of Technology Ladkrabang; Thailand Graduate Institute of Science and Technology; Faculty of Medicine Siriraj Hospital, Mahidol University
License
CC BY
Rights
Author
Publication Source
Scopus