Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress.

Abstract:

:A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high-throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up-regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non-pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Williams KJ,Jenkins VA,Barton GR,Bryant WA,Krishnan N,Robertson BD

doi

10.1111/mmi.13091

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1142-57

issue

6

eissn

0950-382X

issn

1365-2958

journal_volume

97

pub_type

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