Nitrogen starvation-induced transcriptome alterations and influence of transcription regulator mutants in Mycobacterium smegmatis

Abstract

BackgroundAs other bacteria, Mycobacterium smegmatis needs adaption mechanisms to cope with changing nitrogen sources and to survive situations of nitrogen starvation. In the study presented here, transcriptome analyses were used to characterize the response of the bacterium to nitrogen starvation and to elucidate the role of specific transcriptional regulators.ResultsIn response to nitrogen deprivation, a general starvation response is induced in M. smegmatis. This includes changes in the transcription of several hundred genes encoding e.g. transport proteins, proteins involved in nitrogen metabolism and regulation, energy generation and protein turnover. The specific nitrogen-related changes at the transcriptional level depend mainly on the presence of GlnR, while the AmtR protein controls only a small number of genes.ConclusionsM. smegmatis is able to metabolize a number of different nitrogen sources and nitrogen control in M. smegmatis is similar to control mechanisms characterized in streptomycetes, while the master regulator of nitrogen control in corynebacteria, AmtR, is plays a minor role in this regulatory network.

Nitrogen regulator GlnR controls uptake and utilization of non-phosphotransferase-system carbon sources in actinomycetes

“…Previous findings have identified GlnRcontrolled genes involved in carbon and phosphate metabolism, as well as secondary metabolism (19)(20)(21). In the present work, we found that GlnR positively regulates the transport and utilization of multiple sugars in S. erythraea.…”

The pleiotropic transcriptional regulator NlpR contributes to the modulation of nitrogen metabolism, lipogenesis and triacylglycerol accumulation in oleaginous rhodococci

“…The trans_reg_C region containing a helix-turn-helix domain is boxed and putative DNA binding sites are highlighted with asterisks. ortholog) in response to nitrogen starvation, confirming its occurrence as part of the GlnR regulon also in mycobacteria (Jeßberger et al, 2013;Jenkins et al, 2013).…”

“…This global regulator is also absent in corynebacteria. A comprehensive inspection of previous studies revealed that orthologs of nlpR are part of the GlnR regulon in related actinobacteria, such as Streptomyces coelicolor (Amin et al ., ), Mycobacterium smegmatis (Jeßberger et al ., ; Jenkins et al ., ), M. tuberculosis (Williams et al ., ), Amycolatopsis mediterranei (Wang et al ., ) and Saccharopolyspora erythraea (Yao et al ., ).…”

“…Interestingly, the occurrence of NlpR seemed to be restricted to actinobacteria which possess the well-known global regulator of nitrogen metabolism, GlnR. This global regulator is also absent (Amin et al, 2012), Mycobacterium smegmatis (Jeßberger et al, 2013;Jenkins et al, 2013), M. tuberculosis (Williams et al, 2015), Amycolatopsis mediterranei and Saccharopolyspora erythraea (Yao et al, 2014). NlpR-like proteins contain a conserved N-region highly similar to the uroporphyrinogen III synthase enzyme (HemD) and a C-region which resembles an OmpR-like domain associated with regulatory functions.…”

“…Under the control of GlnR, a global regulator of nitrogen metabolism, NnaR acts as a co‐activator of GlnR to control the genes involved in uptake and reduction of /NO 2− in that bacterium (Amin et al ., ). GlnR mutants of Mycobacterium smegmatis showed a significant decreased expression of msmeg_0432 gene ( nnaR ortholog) in response to nitrogen starvation, confirming its occurrence as part of the GlnR regulon also in mycobacteria (Jeßberger et al ., ; Jenkins et al ., ).…”