Open AccessConversion of NO 2 to NO by reduced coenzyme F 420 protects mycobacteria from nitrosative damage
Author(s) -
Endang Purwantini,
Biswarup Mukhopadhyay
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0812883106
Subject(s) - mycobacterium smegmatis , mycobacterium , mycobacterium tuberculosis , cofactor , dehydrogenase , chemistry , strain (injury) , microbiology and biotechnology , biochemistry , phagosome , bacteria , biology , tuberculosis , enzyme , intracellular , medicine , pathology , anatomy , genetics
In mycobacteria, F420 , a deazaflavin derivative, acts as a hydride transfer coenzyme for an F420 -specific glucose-6-phosphate dehydrogenase (Fgd). Physiologically relevant reactions in the mycobacteria that use Fgd-generated reduced F420 (F420 H2 ) are unknown. In this work, F420 H2 was found to be oxidized by NO only in the presence of oxygen. Further analysis demonstrated that NO2 , produced from NO and O2 , was the oxidant. UV-visible spectroscopic and NO-sensor-based analyses proved that F420 H2 reduced NO2 to NO. This reaction could serve as a defense system forMycobacterium tuberculosis , which is more sensitive to NO2 than NO under aerobic conditions. Activated macrophages produce NO, which in acidified phagosomes is converted to NO2 . Hence, by converting NO2 back to NO with F420 H2 ,M. tuberculosis could decrease the effectiveness of antibacterial action of macrophages; such defense would correspond to active tuberculosis conditions where the bacterium grows aerobically. This hypothesis was consistent with the observation that a mutant strain ofMycobacterium smegmatis , a nonpathogenic relative ofM. tuberculosis , which either did not produce or could not reduce F420 , was ≈4-fold more sensitive to NO2 than the wild-type strain. The phenomenon is reminiscent of the anticancer activity of γ-tocopherol, which reduces NO2 to NO and protects human cells from NO2 -induced carcinogenesis.