A Genomic View on Nitrogen Metabolism and Nitrogen Control in Mycobacteria

Abstract

Knowledge about nitrogen metabolism and control in the genus Mycobacterium is sparse, especially compared to the state of knowledge in related actinomycetes like Streptomyces coelicolor or the close relative Corynebacterium glutamicum. Therefore, we screened the published genome sequences of Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium ssp. paratuberculosis and Mycobacterium leprae for genes encoding proteins for uptake of nitrogen sources, nitrogen assimilation and nitrogen control systems, resulting in a detailed comparative genomic analysis of nitrogen metabolism-related genes for all completely sequenced members of the genus. Transporters for ammonium, nitrate, and urea could be identified, as well as enzymes crucial for assimilation of these nitrogen sources, i.e. glutamine synthetase, glutamate dehydrogenase, glutamate synthase, nitrate reductase, nitrite reductase, and urease proteins. A reduction of genes encoding proteins for nitrogen transport and metabolism was observed for the pathogenic mycobacteria, especially for M. leprae. Signal transduction components identified for the different species include adenylyl- and uridylyltransferase and a P_II-type signal transduction protein. Exclusively for M. smegmatis, two homologs of putative nitrogen regulatory proteins were found, namely GlnR and AmtR, while in other mycobacteria, AmtR was absent and GlnR seems to be the nitrogen transcription regulator protein.

E1 of α-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress

“…anaplerotic substrate entering the TCA cycle as α-KG and is also a key intermediate in nitrogen assimilation and metabolism (18,19).…”

The TetR Family of Regulators

“…To date, residues important for this interaction have not been characterized. AmtR homologs are found in Actinobacteria, including some species of Mycobacterium, Nocardia, Rhodococcus, and Streptomyces (25,151). In Streptomyces, two OmpR-like regulators, GlnR and GlnRII, are the master regulators of nitrogen metabolism (152).…”

“…In Streptomyces, two OmpR-like regulators, GlnR and GlnRII, are the master regulators of nitrogen metabolism (152). Although not present in Corynebacterium, GlnR homologs are more conserved in actinobacteria than AmtR homologs; however, there are a few species that encode both (151). Mycobacterium abscessus, Nocardia farcinica, Rhodococcus jostii, Streptomyces avermitilis, and Streptomyces scabies all encode both AmtR and GlnR homologs.…”

Glutamine synthetase encoded by glnA-1 is necessary for cell wall resistance and pathogenicity of Mycobacterium bovis

“…In mycobacteria, GS and glutamate synthetase are the sole means of ammonia assimilation under nitrogenlimiting conditions. Several mycobacterial species are known to possess multiple genetic loci that encode GS (Harper et al, 2008;Amon et al, 2009). Both M. bovis and M. tuberculosis have four different genes encoding GS (Cole et al, 1998;Garnier et al, 2003).…”

“…Disruption of glnA-1 in M. tuberculosis results in glutamine auxotrophy, indicating its role in the synthesis of glutamine for the bacillus (Tullius et al, 2003). The genome of the saprophyte Mycobacterium smegmatis mc 2 155 also contains homologues of glnA-1-4, in addition to several sequences that encode GSs similar to those present in soil-dwelling bacteria but absent from the mycobacterial genome (Amon et al, 2009).…”