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

Abstract

Assimilation of short-chain fatty acids (SCFAs) plays an important role in the survival and lipid biosynthesis of <i>Mycobacteria</i>. 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 <i>Mycobacterium smegmatis</i>, a model <i>Mycobacterium</i>. GlnR can directly activate the expression of <i>MsprpE</i> and <i>Msacs</i> by binding to their promoter regions based upon sensed nitrogen starvation in the host. Moreover, GlnR can activate the expression of lysine acetyltransferase encoding <i>Mspat</i>, 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 <i>M. smegmatis</i> 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 <i>M. smegmatis</i>. These findings provide insights into the survival and nutrient utilization mechanisms of <i>Mycobacteria</i> in their host, which may enable new strategies in drug discovery for the control of tuberculosis.