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Development of an In Vitro Assay for Detection of Drug-Induced Resuscitation-Promoting-Factor-Dependent Mycobacteria.

journal contribution
posted on 01.12.2016, 14:39 by Jessica Loraine, Feifei Pu, Obolbek Turapov, Galina V. Mukamolova
Tuberculosis is a major infectious disease that requires prolonged chemotherapy with a combination of four drugs. Here we present data suggesting that treatment of Mycobacterium tuberculosis, the causative agent of tuberculosis, and Mycobacterium smegmatis, a model organism widely used for the screening of antituberculosis agents, with first-line drugs resulted in the generation of substantial populations that could be recovered only by the addition of a culture supernatant from growing mycobacteria. These bacilli failed to grow in standard media, resulting in significant underestimation of the numbers of viable mycobacteria in treated samples. We generated M. smegmatis strains overexpressing M. tuberculosis resuscitation-promoting factors (Rpfs) and demonstrated their application for the detection of Rpf-dependent mycobacteria generated after drug exposure. Our data offer novel opportunities for validation of the sterilizing activity of antituberculosis agents.

Funding

This work, including the efforts of Jessica Loraine, was funded by Medical Research Council (MRC) (MRC-DTG). This work, including the efforts of Obolbek Turapov, was funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement N115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies= in-kind contribution. This work, including the efforts of Galina V. Mukamolova, was funded by Biotechnology and Biological Sciences Research Council (BBSRC) (BB/H008586/1 and BB/K000330/1).

History

Citation

Antimicrobial Agents and Chemotherapy, 2016, 60 (10), pp. 6227-6233 (7)

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

issn

0066-4804

eissn

1098-6596

Acceptance date

29/07/2016

Copyright date

2016

Available date

01/12/2016

Publisher version

http://aac.asm.org/content/60/10/6227

Notes

Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.00518-16.

Language

en

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