S-nitrosomycothiol reductase and mycothiol are required for survival under aldehyde stress and biofilm formation in Mycobacterium smegmatis.
We show that Mycobacterium smegmatis mutants disrupted in mscR, coding for a dual function S-nitrosomycothiol reductase and formaldehyde dehydrogenase, and mshC, coding for a mycothiol ligase and lacking mycothiol (MSH), are more susceptible to S-nitrosoglutathione (GSNO) and aldehydes than wild type. MSH is a cofactor for MscR, and both mshC and mscR are induced by GSNO and aldehydes. We also show that a mutant disrupted in egtA, coding for a γ-glutamyl cysteine synthetase and lacking in ergothioneine, is sensitive to nitrosative stress but not to aldehydes. In addition, we find that MSH and S-nitrosomycothiol reductase are required for normal biofilm formation in M. smegmatis, suggesting potential new therapeutic pathways to target to inhibit or disrupt biofilm formation. © 2016 IUBMB Life, 68(8):621-628, 2016.
Department of Biology, California State University-Fresno, Fresno, CA, USA.
Derek
D
Vargas
Department of Biology, California State University-Fresno, Fresno, CA, USA.
Samantha
S
Hageman
Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA.
Megha
M
Gulati
Department of Molecular and Cell Biology, University of California Merced, Merced, CA, USA.
Clarissa J
CJ
Nobile
Department of Biology, California State University-Fresno, Fresno, CA, USA.
Mamta
M
Rawat
D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D003545:Cysteine / Q000378:metabolism; D003547:Cysteine Synthase / Q000235:genetics* / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy / Q000382:microbiology*; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000472:pathogenicity; D026403:S-Nitrosothiols / Q000378:metabolism
D000447:Aldehydes; D006020:Glycopeptides; D026403:S-Nitrosothiols; C089265:mycothiol; D007294:Inositol; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; D003547:Cysteine Synthase; D003545:Cysteine
S-nitrosothiol reductase; biofilms; ergothioneine; formaldehyde dehydrogenase; mycobacteria; mycothiol; nitrosative stress