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

Autor:	Yuan Zhang, Li Yuan Zhang, Yu Huang, Jianping Xie, Junqi Xu, Shuang Ma, Kaisar Ali, Yu Chen, Quanxin Long, Xi Mou
Rok vydání:	2020
Předmět:	Microbiology (medical) Transposable element biology Chemistry Mycobacterium smegmatis Mutant Glyoxylate cycle biology.organism_classification Microbiology Molecular biology PncA Efflux NAD+ kinase Mycobacterium
Zdroj:	Future Microbiology. 15:413-426
ISSN:	1746-0921 1746-0913
DOI:	10.2217/fmb-2019-0071
Popis:	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.
Databáze:	OpenAIRE
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