Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Obolbek Turapov; Simon J Waddell; Bernard Burke; Sarah Glenn; Asel A Sarybaeva; Griselda Tudo; Gilles Labesse; Danielle I Young; Michael Young; Peter W Andrew; Philip D Butcher; Martin Cohen-Gonsaud; Galina V Mukamolova

doi:10.1128/AAC.02774-13

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Obolbek Turapov, Simon J Waddell, Bernard Burke, Sarah Glenn, Asel A Sarybaeva, Griselda Tudo, Gilles Labesse, Danielle I Young, Michael Young, Peter W Andrew, Philip D Butcher, Martin Cohen-Gonsaud, Galina V Mukamolova

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Abstract

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.

Original language	English
Pages (from-to)	2798-2806
Number of pages	9
Journal	Antimicrobial Agents and Chemotherapy
Volume	58
Issue number	5
Early online date	10 Apr 2014
DOIs	https://doi.org/10.1128/AAC.02774-13
Publication status	Published - May 2014

Keywords

Animals
Anti-Infective Agents
Cell Line
Electrophoretic Mobility Shift Assay
Fluorescence Polarization
Humans
Mice
Mycobacterium bovis
Mycobacterium tuberculosis
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

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10.1128/AAC.02774-13Licence: CC BY

Turapov_et_alFinal published version, 930 KBLicence: CC BY

Bernard Burke
- Centre for Health and Life Sciences - Associate Professor Research
Person: Teaching and Research

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Turapov, O., Waddell, S. J., Burke, B., Glenn, S., Sarybaeva, A. A., Tudo, G., Labesse, G., Young, D. I., Young, M., Andrew, P. W., Butcher, P. D., Cohen-Gonsaud, M., & Mukamolova, G. V. (2014). Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions. Antimicrobial Agents and Chemotherapy, 58(5), 2798-2806. https://doi.org/10.1128/AAC.02774-13

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title = "Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions",

abstract = "Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.",

keywords = "Animals, Anti-Infective Agents, Cell Line, Electrophoretic Mobility Shift Assay, Fluorescence Polarization, Humans, Mice, Mycobacterium bovis, Mycobacterium tuberculosis, Journal Article, Research Support, Non-U.S. Gov't",

author = "Obolbek Turapov and Waddell, {Simon J} and Bernard Burke and Sarah Glenn and Sarybaeva, {Asel A} and Griselda Tudo and Gilles Labesse and Young, {Danielle I} and Michael Young and Andrew, {Peter W} and Butcher, {Philip D} and Martin Cohen-Gonsaud and Mukamolova, {Galina V}",

year = "2014",

month = may,

doi = "10.1128/AAC.02774-13",

language = "English",

volume = "58",

pages = "2798--2806",

journal = "Antimicrobial Agents and Chemotherapy",

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T1 - Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

AU - Turapov, Obolbek

AU - Waddell, Simon J

AU - Burke, Bernard

AU - Glenn, Sarah

AU - Sarybaeva, Asel A

AU - Tudo, Griselda

AU - Labesse, Gilles

AU - Young, Danielle I

AU - Young, Michael

AU - Andrew, Peter W

AU - Butcher, Philip D

AU - Cohen-Gonsaud, Martin

AU - Mukamolova, Galina V

PY - 2014/5

Y1 - 2014/5

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AB - Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.

KW - Animals

KW - Anti-Infective Agents

KW - Cell Line

KW - Electrophoretic Mobility Shift Assay

KW - Fluorescence Polarization

KW - Humans

KW - Mice

KW - Mycobacterium bovis

KW - Mycobacterium tuberculosis

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1128/AAC.02774-13

DO - 10.1128/AAC.02774-13

M3 - Article

C2 - 24590482

SN - 0066-4804

VL - 58

SP - 2798

EP - 2806

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 5

ER -

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Abstract

Keywords

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Bernard Burke

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