open access

Vol 89, No 2 (2021)
Research paper
Published online: 2021-04-30
Submitted: 2020-11-18
Accepted: 2021-02-04
Get Citation

Comparison of toxin-antitoxin expression among drug-susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis

Hossein Kazemian, Hamid Heidari, Jalil Kardan-Yamchi, Sobhan Ghafourian, Iraj Pakzad, Ebrahim Kouhsari, Hasan Valadbeigi, Nourkhoda Sadeghifard
DOI: 10.5603/ARM.a2021.0033
·
Pubmed: 33966258
·
Adv Respir Med 2021;89(2):110-114.

open access

Vol 89, No 2 (2021)
ORIGINAL PAPERS
Published online: 2021-04-30
Submitted: 2020-11-18
Accepted: 2021-02-04

Abstract

Introduction: Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is a significant global public health threat. Besides extensive multidrug resistance, MTB possesses several properties for long-term viability in the host as well as stress adaptation and resistance in harsh conditions. The role of toxin-antitoxin (TA) systems in disseminating and maintaining antimicrobial resistance in bacterial populations has also been demonstrated. This study aimed to evaluate differences in expression of MazEF (a well-known TA system) related genes (mazE3, mazF3, mazE6, and mazF6) amongst drug-susceptible and resistant MTB isolates in Iran.
Material and methods: A total of 20 confirmed clinical isolates of MTB including 10 drug-susceptible and 10 drug-resistant (nine MDR, and one XDR) species were included in this study. M. tuberculosis H37Rv was used as the standard strain. RNA extraction, cDNA synthesis, and relative quantitative real-time PCR were performed according to the standard procedures.
Results: Our analysis indicated significant enhanced expression of the mazE6 antitoxin gene in drug-susceptible isolates compared to drug-resistant isolates and the standard strain. The expression of the mazF6 toxin gene was also increased in drug-susceptible isolates compared with the standard strain. In drug-resistant isolates, the expression levels of mazF3 and mazF6 genes were significantly higher than that in the susceptible isolates and the standard strain.
Conclusions: In this study, there was significant overexpression of mazE6 in drug-susceptible isolates. As well, mazF3 and F6 were overexpressed in drug-resistant isolates when compared with the standard strain. The changes in expression levels of MazEF6 associated genes were greater than that of MazEF3 in both groups of isolates.

Abstract

Introduction: Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is a significant global public health threat. Besides extensive multidrug resistance, MTB possesses several properties for long-term viability in the host as well as stress adaptation and resistance in harsh conditions. The role of toxin-antitoxin (TA) systems in disseminating and maintaining antimicrobial resistance in bacterial populations has also been demonstrated. This study aimed to evaluate differences in expression of MazEF (a well-known TA system) related genes (mazE3, mazF3, mazE6, and mazF6) amongst drug-susceptible and resistant MTB isolates in Iran.
Material and methods: A total of 20 confirmed clinical isolates of MTB including 10 drug-susceptible and 10 drug-resistant (nine MDR, and one XDR) species were included in this study. M. tuberculosis H37Rv was used as the standard strain. RNA extraction, cDNA synthesis, and relative quantitative real-time PCR were performed according to the standard procedures.
Results: Our analysis indicated significant enhanced expression of the mazE6 antitoxin gene in drug-susceptible isolates compared to drug-resistant isolates and the standard strain. The expression of the mazF6 toxin gene was also increased in drug-susceptible isolates compared with the standard strain. In drug-resistant isolates, the expression levels of mazF3 and mazF6 genes were significantly higher than that in the susceptible isolates and the standard strain.
Conclusions: In this study, there was significant overexpression of mazE6 in drug-susceptible isolates. As well, mazF3 and F6 were overexpressed in drug-resistant isolates when compared with the standard strain. The changes in expression levels of MazEF6 associated genes were greater than that of MazEF3 in both groups of isolates.

Get Citation

Keywords

Mycobacterium tuberculosis; Toxin-Antitoxin (TA) system; MazEF; gene expression

Supp./Additional Files (1)
Supplementary Files
Download
436KB
About this article
Title

Comparison of toxin-antitoxin expression among drug-susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis

Journal

Advances in Respiratory Medicine

Issue

Vol 89, No 2 (2021)

Article type

Research paper

Pages

110-114

Published online

2021-04-30

DOI

10.5603/ARM.a2021.0033

Pubmed

33966258

Bibliographic record

Adv Respir Med 2021;89(2):110-114.

Keywords

Mycobacterium tuberculosis
Toxin-Antitoxin (TA) system
MazEF
gene expression

Authors

Hossein Kazemian
Hamid Heidari
Jalil Kardan-Yamchi
Sobhan Ghafourian
Iraj Pakzad
Ebrahim Kouhsari
Hasan Valadbeigi
Nourkhoda Sadeghifard

References (18)
  1. Howard NC, Marin ND, Ahmed M, et al. Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation reprograms macrophage metabolism through cell wall lipid changes. Nat Microbiol. 2018; 3(10): 1099–1108.
  2. Raviglione M, Sulis G. Tuberculosis 2015: burden, challenges and strategy for control and elimination. Infect Dis Rep. 2016; 8(2): 6570.
  3. Nguyen TN, Anton-Le Berre V, Bañuls AL, et al. Molecular diagnosis of drug-resistant tuberculosis; a literature review. Front Microbiol. 2019; 10: 794.
  4. Zhai W, Wu F, Zhang Y, et al. The immune escape mechanisms of . Int J Mol Sci. 2019; 20(2).
  5. Tiwari P, Arora G, Singh M, et al. MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs. Nat Commun. 2015; 6: 6059.
  6. Korch SB, Malhotra V, Contreras H, et al. The Mycobacterium tuberculosis relBE toxin:antitoxin genes are stress-responsive modules that regulate growth through translation inhibition. J Microbiol. 2015; 53(11): 783–795.
  7. Slayden RA, Dawson CC, Cummings JE, et al. MazF6 toxin of Mycobacterium tuberculosis demonstrates antitoxin specificity and is coupled to regulation of cell growth by a Soj-like protein. BMC Microbiol. 2013; 13(4): 240.
  8. Deep A, Tiwari P, Agarwal S, et al. Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation. Nucleic Acids Res. 2018; 46(21): 11639–11655.
  9. Fernández-García L, Blasco L, Lopez M, et al. Toxin-Antitoxin systems in clinical pathogens. Toxins (Basel). 2016; 8(7).
  10. Gupta A, Venkataraman B, Vasudevan M, et al. Co-expression network analysis of toxin-antitoxin loci in Mycobacterium tuberculosis reveals key modulators of cellular stress. Sci Rep. 2017; 7(1): 5868.
  11. Yang QE, Walsh TR. Toxin-antitoxin systems and their role in disseminating and maintaining antimicrobial resistance. FEMS Microbiol Rev. 2017; 41(3): 343–353.
  12. Zhao JL, Liu W, Xie WY, et al. Viability, biofilm formation, and MazEF expression in drug-sensitive and drug-resistant strains circulating in Xinjiang, China. Infect Drug Resist. 2018; 11: 345–358.
  13. Coskun US, Cicek AC, Kilinc C, et al. Effect of mazEF, higBA and relBE toxin-antitoxin systems on antibiotic resistance in Pseudomonas aeruginosa and Staphylococcus isolates. Malawi Med J. 2018; 30(2): 67–72.
  14. Kardan Yamchi J, Haeili M, Gizaw Feyisa S, et al. Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran. Infect Genet Evol. 2015; 36: 23–26.
  15. Koch A, Cox H, Mizrahi V. Drug-resistant tuberculosis: challenges and opportunities for diagnosis and treatment. Curr Opin Pharmacol. 2018; 42: 7–15.
  16. Sala A, Bordes P, Genevaux P. Multiple toxin-antitoxin systems in Mycobacterium tuberculosis. Toxins (Basel). 2014; 6(3): 1002–1020.
  17. Caño-Muñiz S, Anthony R, Niemann S, et al. New approaches and therapeutic options for mycobacterium tuberculosis in a dormant state. Clin Microbiol Rev. 2018; 31(1).
  18. Kędzierska B, Hayes F. Emerging roles of toxin-antitoxin modules in bacterial pathogenesis. Molecules. 2016; 21(6).

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Pneumonologia i Alergologia Polska dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl