Regulatory RNA in Mycobacterium tuberculosis, back to basics

Schwenk, Stefan; Arnvig, Kristine B.

doi:10.1093/femspd/fty035

Cited by 38 publications

(51 citation statements)

References 115 publications

(138 reference statements)

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“…Although not yet experimentally validated, the M. tuberculosis ydaO switch is predicted to be a cyclic-di-AMP sensing OFF switch, similar to the ones found in B. subtilis and Streptomyces coelicolor [50][51][52]. Whether this leads to Rho-dependent termination of transcription remains to be seen.…”

Section: Different Riboswitches Regulating the Expression Of Homologomentioning

confidence: 84%

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Riboswitches: choosing the best platform

Arnvig

2019

Biochemical Society Transactions

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Riboswitch discovery and characterisation have come a long way since the term was first coined almost two decades ago. Riboswitches themselves are likely derived from ancient ligand-binding transcripts, which have evolved into sophisticated genetic control elements that are widespread in prokaryotes. Riboswitches are associated with a multitude of cellular processes including biosynthetic pathways, transport mechanisms and stress responses leading to an ever-increasing appreciation for an in-depth understanding of their triggers and functions in order to address physiological and regulatory questions. The majority of riboswitches exert their control via transcriptional or translational expression platforms depending on their genetic context. It remains, however, to be determined precisely why one platform is favoured over another. Is this a question of the layout of the gene expression machinery, ligand availability, the degree of control required, serendipity or various combinations of these? With this review, rather than providing answers, I am hoping to plant a seed for further scientific discussions about this puzzle.

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Section: Different Riboswitches Regulating the Expression Of Homologomentioning

confidence: 84%

“…Judging by the absence of a canonical intrinsic terminator, ydaO employs the translational platform generally preferred by M. tuberculosis, while rpfB has been shown experimentally to employ a transcriptional platform [8,50].…”

Section: Different Riboswitches Regulating the Expression Of Homologomentioning

confidence: 99%

Riboswitches: choosing the best platform

Arnvig

2019

Biochemical Society Transactions

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“…Rpfs are transglycosylases, and hence it was suggested that they act by remodeling peptidoglycan structure ( Cohen-Gonsaud et al., 2005 ). Rpfs are thought to be required for virulence, suggesting that remodeling of M. tuberculosis peptidoglycan is important during infection ( Kana et al., 2008 ; Rosser et al., 2017 ), and their expression is tightly regulated both transcriptionally and post-transcriptionally ( Schwenk and Arnvig, 2018 ). Among the complex repertoire of proteins involved in regulating peptidoglycan synthesis in M. tuberculosis is CwlM, an essential cytoplasmic protein similar to peptidoglycan amidases ( Boutte et al., 2016 ; Turapov et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Coupling of Peptidoglycan Synthesis to Central Metabolism in Mycobacteria: Post-transcriptional Control of CwlM by Aconitase

et al. 2020

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Summary Mycobacterium tuberculosis causes human tuberculosis, and a better understanding of its biology is required to identify vulnerabilities that might be exploited in developing new therapeutics. The iron-sulfur cluster of the essential M. tuberculosis central metabolic enzyme, aconitase (AcnA), disassembles when exposed to oxidative/nitrosative stress or iron chelators. The catalytically inactive apo-AcnA interacts with a sequence resembling an iron-responsive element (IRE) located within the transcript of another essential protein, CwlM, a regulator of peptidoglycan synthesis. A Mycobacterium smegmatis cwlM conditional mutant complemented with M. tuberculosis cwlM with a disrupted IRE is unable to recover from combinations of oxidative, nitrosative, and iron starvation stresses. An equivalent M. tuberculosis cwlM conditional mutant complemented with the cwlM gene lacking a functional IRE exhibits a growth defect in THP-1 macrophages. It appears that AcnA acts to couple peptidoglycan synthesis and central metabolism, and disruption of this coupling potentially leaves mycobacteria vulnerable to attack by macrophages.

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“…Application of the high throughput sequencing and computer algorithm approaches allowed identification of dozens of sRNAs in mycobacterial species (Haning et al, 2014; Schwenk and Arnvig, 2018; Taneja and Dutta, 2019). Several in vitro studies have elucidated the functioning of sRNAs in M. tuberculosis (Arnvig et al, 2011; Solans et al, 2014; Moores et al, 2017; Gerrick et al, 2018; Mai et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages

Salina¹,

Grigorov

Skvortsova

et al. 2019

Front. Cell. Infect. Microbiol.

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Small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. We investigated the dynamics of expression of MTS1338, a small non-coding RNA of Mycobacterium tuberculosis, in the mouse model in vivo, regulation of its expression in the infected macrophages, and the consequences of its overexpression in bacterial cultures. Here we demonstrate that MTS1338 significantly contributes to host-pathogen interactions. Activation of the host immune system triggered NO-inducible up-regulation of MTS1338 in macrophage-engulfed mycobacteria. Constitutive overexpression of MTS1338 in cultured mycobacteria improved their survival in vitro under low pH conditions. MTS1338 up-regulation launched a spectrum of shifts in the transcriptome profile similar to those reported for M. tuberculosis adaptation to hostile intra-macrophage environment. Using the RNA-seq approach, we demonstrate that gene expression changes accompanying MTS1338 overexpression indicate reduction in translational activity and bacterial growth. These changes indicate mycobacteria entering the dormant state. Taken together, our results suggest a direct involvement of this sRNA in the interplay between mycobacteria and the host immune system during infectious process.

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Regulatory RNA in Mycobacterium tuberculosis, back to basics

Cited by 38 publications

References 115 publications

Riboswitches: choosing the best platform

Riboswitches: choosing the best platform

Coupling of Peptidoglycan Synthesis to Central Metabolism in Mycobacteria: Post-transcriptional Control of CwlM by Aconitase

MTS1338, A Small Mycobacterium tuberculosis RNA, Regulates Transcriptional Shifts Consistent With Bacterial Adaptation for Entering Into Dormancy and Survival Within Host Macrophages

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