Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD+/NADH dysregulation
- 1 April 2020
- journal article
- research article
- Published by Future Medicine Ltd in Future Microbiology
- Vol. 15 (6), 413-426
- https://doi.org/10.2217/fmb-2019-0071
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 mc(2)155 transposon library using 50 mu M 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 degrees 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.This publication has 44 references indexed in Scilit:
- Pyrazinamide resistance among drug-resistant Mycobacterium tuberculosis isolates at a referral hospitalDiagnostic Microbiology and Infectious Disease, 2013
- gyrA/B fluoroquinolone resistance allele profiles amongst Mycobacterium tuberculosis isolates from mainland ChinaInternational Journal of Antimicrobial Agents, 2012
- Pyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosisScience, 2011
- Contribution of Oxidative Damage to Antimicrobial LethalityAntimicrobial Agents and Chemotherapy, 2009
- Demonstration of intrinsic efflux activity of Escherichia coli K-12 AG100 by an automated ethidium bromide methodInternational Journal of Antimicrobial Agents, 2008
- A central role for the peroxisomal membrane in glyoxylate cycle functionBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2006
- The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of MetabolismJournal of Biological Chemistry, 2004
- Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acidJournal of Antimicrobial Chemotherapy, 2003
- Escherichia coligenes involved in resistance to pyrazinoic acid, the active component of the tuberculosis drug pyrazinamideFEMS Microbiology Letters, 2002
- The pncA gene from naturally pyrazinamide-resistant Mycobacterium avium encodes pyrazinamidase and confers pyrazinamide susceptibility to resistant M. tuberculosis complex organismsMicrobiology, 1997