@article { ISI:000300864500001,
	title = {Nitrate reduction pathways in mycobacteria and their implications during latency},
	journal = {Microbiology-SGM},
	volume = {158},
	number = {2},
	year = {2012},
	month = {FEB},
	pages = {301-307},
	publisher = {SOC GENERAL MICROBIOLOGY},
	address = {MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND},
	abstract = {<p>Mycobacterial persistence has gained a lot of attention with respect to developing novel antitubercular drugs, which could drastically reduce the duration of tuberculosis (TB) therapy. A better understanding of the physiology of Mycobacterium tuberculosis, and of the metabolic state of the bacillus during the latent period, is a primary need in finding drug targets against persistent TB. Recent biochemical and genetic studies of nitrate reduction in mycobacteria have revealed the roles of distinct proteins and enzymes involved in the pathway. The differential degree of nitrate reduction among pathogenic and non-pathogenic mycobacterial species, and its regulation during oxygen and nutrient limitation, suggest a link between nitrate reduction pathways and latency. The respiratory and assimilatory reduction of nitrate in mycobacteria may be interconnected to facilitate rapid adaptation to changing oxygen and/or nitrogen conditions, increasing metabolic flexibility for survival in the hostile host environment. This review summarizes the nitrate metabolic pathways operative in mycobacteria to provide an insight into the mechanisms that M. tuberculosis has evolved to adapt successfully to the host environment.</p>},
	issn = {1350-0872},
	doi = {10.1099/mic.0.054759-0},
	author = {Khan, Arshad and Sarkar, Dhiman}
}
@article { ISI:000324909200005,
	title = {Nitrite reductase NirBD is induced and plays an important role during in vitro dormancy of mycobacterium tuberculosis},
	journal = {Journal of Bacteriology},
	volume = {195},
	number = {20},
	year = {2013},
	month = {OCT},
	pages = {4592-4599},
	publisher = {AMER SOC MICROBIOLOGY},
	address = {1752 N ST NW, WASHINGTON, DC 20036-2904 USA},
	abstract = {<p>Mycobacterium tuberculosis is one of the strongest reducers of nitrate among all mycobacteria. Reduction of nitrate to nitrite, mediated by nitrate reductase (NarGHJI) of M. tuberculosis, is induced during the dormant stage, and the enzyme has a respiratory function in the absence of oxygen. Nitrite reductase (NirBD) is also functional during aerobic growth when nitrite is the sole nitrogen source. However, the role of NirBD-mediated nitrite reduction during the dormancy is not yet characterized. Here, we analyzed nitrite reduction during aerobic growth as well as in a hypoxic dormancy model of M. tuberculosis in vitro. When nitrite was used as the sole nitrogen source in the medium, the organism grew and the reduction of nitrite was evident in both hypoxic and aerobic cultures of M. tuberculosis. Remarkably, the hypoxic culture of M. tuberculosis, compared to the aerobic culture, showed 32- and 4-fold-increased expression of nitrite reductase (NirBD) at the transcription and protein levels, respectively. More importantly, a nirBD mutant of M. tuberculosis was unable to reduce nitrite and compared to the wild-type (WT) strain had a \&gt;2-log reduction in viability after 240 h in the Wayne model of hypoxic dormancy. Dependence of M. tuberculosis on nitrite reductase (NirBD) was also seen in a human macrophage-based dormancy model where the nirBD mutant was impaired for survival compared to the WT strain. Overall, the increased expression and essentiality of nitrite reductase in the in vitro dormancy models suggested that NirBD-mediated nitrite reduction could be critical during the persistent stage of M. tuberculosis.</p>},
	issn = {0021-9193},
	doi = {10.1128/JB.00698-13},
	author = {Akhtar, Shamim and Khan, Arshad and Sohaskey, Charles D. and Jagannath, Chinnaswamy and Sarkar, Dhiman}
}
