AUTHOR=Liu Xin-Xin , Shen Meng-Jia , Liu Wei-Bing , Ye Bang-Ce 

TITLE=GlnR-Mediated Regulation of Short-Chain Fatty Acid Assimilation in Mycobacterium smegmatis

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01311

DOI=10.3389/fmicb.2018.01311

ISSN=1664-302X

ABSTRACT=<p>Assimilation of short-chain fatty acids (SCFAs) plays an important role in the survival and lipid biosynthesis of <italic>Mycobacteria</italic>. However, regulation of this process has not been thoroughly described. In the present work, we demonstrate that GlnR as a well-known nitrogen-sensing regulator transcriptionally modulates the AMP-forming propionyl-CoA synthetase (MsPrpE), and acetyl-CoA synthetases (MsAcs) is associated with SCFAs assimilation in <italic>Mycobacterium smegmatis</italic>, a model <italic>Mycobacterium</italic>. GlnR can directly activate the expression of <italic>MsprpE</italic> and <italic>Msacs</italic> by binding to their promoter regions based upon sensed nitrogen starvation in the host. Moreover, GlnR can activate the expression of lysine acetyltransferase encoding <italic>Mspat</italic>, which significantly decreases the activity of MsPrpE and MsAcs through increased acylation. Next, growth curves and resazurin assay show that GlnR can further regulate the growth of <italic>M. smegmatis</italic> on different SCFAs to control the viability. These results demonstrate that GlnR-mediated regulation of SCFA assimilation in response to the change of nitrogen signal serves to control the survival of <italic>M. smegmatis</italic>. These findings provide insights into the survival and nutrient utilization mechanisms of <italic>Mycobacteria</italic> in their host, which may enable new strategies in drug discovery for the control of tuberculosis.</p>