Skip to main content
Top
Published in: Antimicrobial Resistance & Infection Control 1/2017

Open Access 01-12-2017 | Research

Sub-minimum inhibitory concentration of rifampin: a potential risk factor for resuscitation of Mycobacterium tuberculosis

Authors: Shahin Pourazar Dizaji, Alireza Taala, Morteza Masoumi, Nayereh Ebrahimzadeh, Abolfazl Fateh, Seyed Davar Siadat, Farzam Vaziri

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2017

Login to get access

Abstract

Background

Mycobacterium tuberculosis possesses five resuscitation-promoting factors, Rpf A to E, which are required for the resuscitation of dormancy in mycobacteria. This study explores the transcriptional profile of all five rpfs of M. tuberculosis, in response to sub-MIC concentration of rifampin, in multidrug and mono-rifampin resistant clinical isolates.

Methods

Thirteen multidrug and two rifampin mono resistant clinical isolates were analyzed. Drug susceptibility testing and determination of MIC were performed. The relative expression of rpfs was measured, by real-time quantitative PCR.

Results

A significant upregulation of relative expression (p < 0.05) was observed, as follows: 7/15(46.66%); 5/15(33.33%); 9/15(60%); 10/15(66.66%) and 9/15(60%) in rpfA, rpfB, rpfC, rpfD and rpfE, respectively.

Conclusion

Our results showed that the rpfs could be overexpressed in some extent in the presence of sub-MIC concentration of rifampin in multidrug and mono drug resistant M. tuberculosis. These results highlight the potential risk of sub-MIC rifampin concentrations, as a risk factor for tuberculosis reactivation.
Literature
1.
go back to reference Magombedze G, Dowdy D, Mulder N. Latent tuberculosis: models, Computational Efforts and the Pathogen's Regulatory Mechanisms during Dormancy. Front Bioeng Biotechnol. 2013;1:4. eCollection 2013CrossRefPubMedPubMedCentral Magombedze G, Dowdy D, Mulder N. Latent tuberculosis: models, Computational Efforts and the Pathogen's Regulatory Mechanisms during Dormancy. Front Bioeng Biotechnol. 2013;1:4. eCollection 2013CrossRefPubMedPubMedCentral
2.
go back to reference World Health Organization. 2014. Global tuberculosis report 2014. World Health Organization. 2014. Global tuberculosis report 2014.
6.
go back to reference Chauviac FX, Robertson G, Quay DH, Bagnéris C, Dumas C, Henderson B, Ward J, Keep NH, Cohen-Gonsaud M. The RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation-promoting factor catalytic domain. Acta Crystallogr F Struct Biol Commun. 2014;70(Pt 8):1022–6. doi:10.1107/S2053230X1401317X. CrossRefPubMedPubMedCentral Chauviac FX, Robertson G, Quay DH, Bagnéris C, Dumas C, Henderson B, Ward J, Keep NH, Cohen-Gonsaud M. The RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation-promoting factor catalytic domain. Acta Crystallogr F Struct Biol Commun. 2014;70(Pt 8):1022–6. doi:10.​1107/​S2053230X1401317​X.​ CrossRefPubMedPubMedCentral
7.
go back to reference Kaprelyants AS, Mukamolova GV, Ruggiero A, Makarov VA, Demina GR, Shleeva MO, Potapov VD, Shramko PA. Resuscitation-promoting factors (Rpf): in search of inhibitors. Protein Pept Lett. 2012;19(10):1026–34.CrossRefPubMed Kaprelyants AS, Mukamolova GV, Ruggiero A, Makarov VA, Demina GR, Shleeva MO, Potapov VD, Shramko PA. Resuscitation-promoting factors (Rpf): in search of inhibitors. Protein Pept Lett. 2012;19(10):1026–34.CrossRefPubMed
10.
go back to reference Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, Meissner G, Mitchison DA, Sula L. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ. 1963;29:565–78.PubMedPubMedCentral Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, Meissner G, Mitchison DA, Sula L. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ. 1963;29:565–78.PubMedPubMedCentral
11.
go back to reference Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2002;46(8):2720–2.CrossRefPubMedPubMedCentral Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2002;46(8):2720–2.CrossRefPubMedPubMedCentral
13.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
14.
go back to reference Zhao S, Song X, Zhao Y, Qiu Y, Mao F, Zhang C, Bai B, Zhang H, Wu S, Shi C. Protective and therapeutic effects of the resuscitation-promoting factor domain and its mutants against Mycobacterium tuberculosis in mice. Pathog Dis. 2015;73(3):pii: ftu025. doi:10.1093/femspd/ftu025.CrossRef Zhao S, Song X, Zhao Y, Qiu Y, Mao F, Zhang C, Bai B, Zhang H, Wu S, Shi C. Protective and therapeutic effects of the resuscitation-promoting factor domain and its mutants against Mycobacterium tuberculosis in mice. Pathog Dis. 2015;73(3):pii: ftu025. doi:10.​1093/​femspd/​ftu025.CrossRef
19.
20.
go back to reference Rosser A, Stover C, Pareek M, Mukamolova GV. Resuscitation-promoting factors are important determinants of the pathophysiology in Mycobacterium tuberculosis infection. Crit Rev Microbiol. 2017:1–10. doi:10.1080/1040841X.2017.1283485. Rosser A, Stover C, Pareek M, Mukamolova GV. Resuscitation-promoting factors are important determinants of the pathophysiology in Mycobacterium tuberculosis infection. Crit Rev Microbiol. 2017:1–10. doi:10.​1080/​1040841X.​2017.​1283485.
22.
go back to reference Turapov O, O'Connor BD, Sarybaeva AA, Williams C, Patel H, Kadyrov AS, Sarybaev AS, Woltmann G, Barer MR, Mukamolova GV. Phenotypically adapted Mycobacterium tuberculosis populations from sputum are tolerant to first-line drugs. Antimicrob Agents Chemother. 2016;60(4):2476–83. doi:10.1128/AAC.01380-15.CrossRefPubMedPubMedCentral Turapov O, O'Connor BD, Sarybaeva AA, Williams C, Patel H, Kadyrov AS, Sarybaev AS, Woltmann G, Barer MR, Mukamolova GV. Phenotypically adapted Mycobacterium tuberculosis populations from sputum are tolerant to first-line drugs. Antimicrob Agents Chemother. 2016;60(4):2476–83. doi:10.​1128/​AAC.​01380-15.CrossRefPubMedPubMedCentral
25.
go back to reference Tufariello JM, Mi K, Xu J, Manabe YC, Kesavan AK, Drumm J, Tanaka K, Jacobs WR Jr, Chan J. Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis. Infect Immun 2006;74(5):2985–2995. Tufariello JM, Mi K, Xu J, Manabe YC, Kesavan AK, Drumm J, Tanaka K, Jacobs WR Jr, Chan J. Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009 gene results in delayed reactivation from chronic tuberculosis. Infect Immun 2006;74(5):2985–2995.
27.
go back to reference Veatch AV, Kaushal D. Opening Pandora's Box: Mechanisms of Mycobacterium tuberculosis resuscitation. Trends Microbiol 2017 pii: S0966-842X (17)30191–30199 doi:10.1016/jtim201708.001. Veatch AV, Kaushal D. Opening Pandora's Box: Mechanisms of Mycobacterium tuberculosis resuscitation. Trends Microbiol 2017 pii: S0966-842X (17)30191–30199 doi:10.​1016/​jtim201708.​001.
Metadata
Title
Sub-minimum inhibitory concentration of rifampin: a potential risk factor for resuscitation of Mycobacterium tuberculosis
Authors
Shahin Pourazar Dizaji
Alireza Taala
Morteza Masoumi
Nayereh Ebrahimzadeh
Abolfazl Fateh
Seyed Davar Siadat
Farzam Vaziri
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Antimicrobial Resistance & Infection Control / Issue 1/2017
Electronic ISSN: 2047-2994
DOI
https://doi.org/10.1186/s13756-017-0273-1

Other articles of this Issue 1/2017

Antimicrobial Resistance & Infection Control 1/2017 Go to the issue