Research Article

Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD⁺/NADH dysregulation

Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment & Bio-Resource of The Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China

^‡Authors contributed equally

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Yu Chen^‡

Shenyang Tenth People’s Hospital (Shenyang Chest Hospital), Dadong District, Shenyang City, Liaoning 110044, China

^‡Authors contributed equally

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Xi Mou

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Yu Huang

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Shuang Ma

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Liyuan Zhang

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Yuan Zhang

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Quanxin Long

The Second Affiliated Hospital & the Key Laboratory of Molecular Biology of Infectious Diseases of The Ministry of Education, Chongqing Medical University, Yuzhong District, Chongqing 400016, China

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Md Kaisar Ali

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Jianping Xie

*Author for correspondence:

E-mail Address: georgex@swu.edu.cn

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Published Online:6 Apr 2020https://doi.org/10.2217/fmb-2019-0071

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Abstract

Aim: To identify and characterize new mycobacterium pyrazinamide (PZA) resistance genes in addition to pncA, rpsA and panD. Materials & methods: To screen a Tn7 M. smegmatis mc²155 transposon library using 50 μM PZA and a PZA hypersensitive mutant (M492) was obtained. MIC was further used to confirm the hypersensitivity of M492 mutant by culturing the mutant in Middlebrook 7H9 liquid medium at 37°C. Results:msmeg_3314 is the gene underlying the hypersensitive phenotype of mutant M492. The observed resistance to PZA and fluoroquinolones involved the alteration of Mycobacterium cell wall permeability and the dissipation of the proton motive force. NAD⁺/NADH dysregulation and attenuated glyoxylate shunt might underlie the declined scavenging capacity of reactive oxygen species in the msmeg_3314-deficient mutants. Conclusion:msmeg_ 3314 is a novel gene involved in pyrazinamide resistance and might be a new candidate for drugs target.

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Vol. 15, No. 6

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Received 8 March 2019

Accepted 25 February 2020

Published online 6 April 2020

Published in print April 2020

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fmb-2019-0071

Author contributions

J Xu, Y Chen, X Mou, Y Huang, S Ma, L Zhang, Y Zhang, Q Long, M Ali and J Xie analyzed the data. J Xu, Y Chen and J Xie designed the study and wrote the paper. All authors have read and approved the manuscript.

Financial & competing interests disclosure

This work was supported by National Natural Science Foundation (grant number 81871182). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funded writing assistance was utilized in study design, data collection and interpretation of the results, or the decision to submit the work for publication.

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Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD+/NADH dysregulation

Abstract

References

Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD⁺/NADH dysregulation