Regulatory and pathogenesis roles of Mycobacterium Lrp/AsnC family transcriptional factors

Abstract

Lrp/AsnC (leucine-responsive regulatory protein/asparagine synthase C products) family transcriptional regulators, widespread among bacteria and archaea, is also known as feast/famine regulatory protein (FFRPs). They regulate multiple cellular metabolisms globally (Lrp) or specifically (AsnC), such as amino acid metabolism, pili synthesis, DNA transactions during DNA repair and recombination, and also might be implicated in persistence. To better understanding of the pathogenesis of M. tuberculosis, based on our lab's work on this transcriptional factor family, these progresses are summarized, with special focus on that of Mycobacterium via comparative genomics.

The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates APC function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism

“…In addition, Lrp/AsnC proteins take part in various metabolic processes in fungi and bacteria. 43,44 Here, our data show that recombinant leucine-responsive regulatory protein (rLrp) dampens TLR signaling by interfering with the assembly of the MyD88-dependent signaling scaffold. RLrp binding to TLR2-activated PI3K-protein kinase b (Akt)-dependent signaling and inhibited LPS-induced cytokine production and NF-kB activation by blocking IRAK1, TRAF6, and TAK1 signalosome formation.…”

An overview on transcriptional regulators in Streptomyces

“…In all known crystal structures, this linker is well conserved, sug-472 gesting conformational rigidity to some extent [58,203]. Most Lrp/AsnC 473 transcription factors studied so far are able to self-regulate (positively or 474 negatively) [58]. The E. coli Lrp protein is largely considered a global 475 transcription factor [165], suggesting that these proteins play an indis- …”

“…The asparagine synthase C (AsnC), which is involved 458 in asparagine biosynthesis [58,137] [218]. In all known crystal structures, this linker is well conserved, sug-472 gesting conformational rigidity to some extent [58,203].…”

Biochemical Characterization of Isoniazid-resistant Mycobacterium tuberculosis: Can the Analysis of Clonal Strains Reveal Novel Targetable Pathways?

“…Little is known about Rv3050c.1 that is part of the AsnC-family which groups regulators specifically triggered by asparagine binding. Among the possible events regulated by this protein are amino acid metabolism, DNA repair, central carbon metabolism and persistence [37]. Lastly, the regulatory protein Rv3676, was found with increased abundance in our study for our clinical isolate, and was also shown to be an important regulatory protein via transcriptomic studies in response to hypoxia and/or nutrient starvation that include discordant results similar to ours, which may be explained by differences between strains [36,38,39] Increased higher levels of AhpC were concomitant with a non-significantly altered virulent bacterial phenotype [6].…”