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

2020 ◽  
Vol 15 (6) ◽  
pp. 413-426
Author(s):  
Junqi Xu ◽  
Yu Chen ◽  
Xi Mou ◽  
Yu Huang ◽  
Shuang Ma ◽  
...  

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.

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Cindy Wang ◽  
Engy A. Mahrous ◽  
Richard E. Lee ◽  
Martha M. Vestling ◽  
Kuni Takayama

The addition of polyoxyethylene sorbitan monooleate (Tween 80) to a culture of mycobacteria greatly influences cell permeability and sensitivity to antibiotics but very little is known regarding the underlying mechanism. Here we show thatCorynebacterium matruchotii(surrogate of mycobacteria) converts Tween 80 to a structural series of polyoxyethylenic acids which are then used to form novel series-2A and series-2B glycolipids. Minor series-3 glycolipids were also synthesized. The polyoxyethylenic acids replaced corynomycolic acids in the cell wall. Correspondingly the trehalose dicorynomycolate content was reduced. MALDI mass spectrometry, MS-MS,1H-NMR, and13C-NMR were used to characterize the series-2 glycolipids. Series-2A glycolipid is trehalose 6-C36:2-corynomycolate-6′-polyoxyethylenate and series-2B glycolipid is trehalose 6-C36:2-corynomycolate-6′-furan ring-containing polyoxyethylenate.Mycobacterium smegmatisgrown in the presence of Tween 80 also synthesizes series-2 type glycolipids. The synthesis of these novel glycolipids in corynebacteria and mycobacteria should result in gross changes in the cell wall permeability and drug sensitivity.


2021 ◽  
Author(s):  
Yanrong Huang ◽  
Sushil Dhital ◽  
Feitong Liu ◽  
Xiong Fu ◽  
Qiang Huang ◽  
...  

Processing induced structural changes of whole foods on regulation of colonic fermentation rate and microbiota composition are least understood and often overlooked. In the present study, intact cotyledon cells from...


2011 ◽  
Vol 156 (3) ◽  
pp. 1364-1374 ◽  
Author(s):  
Lucinda Denness ◽  
Joseph Francis McKenna ◽  
Cecile Segonzac ◽  
Alexandra Wormit ◽  
Priya Madhou ◽  
...  

2009 ◽  
Vol 1790 (10) ◽  
pp. 1307-1313 ◽  
Author(s):  
Fernando G. Dupuy ◽  
María V. Niklison Chirou ◽  
Beatriz Fernández de Arcuri ◽  
Carlos J. Minahk ◽  
Roberto D. Morero

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