The Partner Switching System of the SigF Sigma Factor in Mycobacterium smegmatis and Induction of the SigF Regulon Under Respiration-Inhibitory Conditions

Oh, Yuna; Song, Su-Yeon; Kim, Hyejun; Han, Gil Soo; Hwang, Jihwan; Kang, Houyang; Oh, Jun-Hyok

doi:10.3389/fmicb.2020.588487

Cited by 11 publications

(25 citation statements)

References 61 publications

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“…We analyzed gene expression of M. abscessus subsp . abscessus grown in 7H9 medium supplemented with OADC 40 , M. smegmatis grown in 7H9 medium with glucose 41 , and three experiments performed with M. tuberculosis H37Rv grown in 7H9 broth supplemented with OADC 20 , in a medium supplemented with cholesterol as a sole carbon source 21 and in human THP-1 derived macrophages three days post-infection. Each experiment contained data for three replicates.…”

Section: Methodsmentioning

confidence: 99%

Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis

Minias

Gąsior

Brzostek

et al. 2021

Sci Rep

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Cobalamin (vitamin B12) is a structurally complex molecule that acts as a cofactor for enzymes and regulates gene expression through so-called riboswitches. The existing literature on the vitamin B12 synthesis capacity in Mycobacterium tuberculosis is ambiguous, while in non-tuberculous mycobacteria (NTM) is rather marginal. Here we present the results of our investigation into the occurrence of vitamin B12 in mycobacteria. For detection purposes, immunoassay methods were applied to cell lysates of NTM and M. tuberculosis clinical and laboratory strains grown under different conditions. We show that whereas vitamin B12 is present in cells of various NTM species, it cannot be evidenced in strains of differently cultured M. tuberculosis, even though the genes responsible for vitamin B12 synthesis are actively expressed based on RNA-Seq data. In summary, we conclude that the production of vitamin B12 does occur in mycobacteria, with the likely exception of M. tuberculosis. Our results provide direct evidence of vitamin B12 synthesis in a clinically important group of bacteria.

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Section: Methodsmentioning

confidence: 99%

Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis

Minias

Gąsior

Brzostek

et al. 2021

Sci Rep

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“…RsfA-like proteins are present only in mycobacterial species that cause tuberculosis, suggesting a possible role for these proteins in virulence ( Beaucher et al., 2002 ; Manganelli et al., 2004 ). In M. smegmatis , RsfA has been shown to interact more strongly with RsbW1 than RsfB ( Singh et al., 2015 ), and acts as a stronger anti-σ F antagonist than RsfB ( Oh et al., 2020 ). A serine residue at position 63 of RsfB of M. smegmatis , and its phosphorylation by RsbW2, determines the functionality of RsfB as an anti-sigma antagonist.…”

Section: Canonical Stas Domain Only Proteinsmentioning

confidence: 99%

“…A serine residue at position 63 of RsfB of M. smegmatis , and its phosphorylation by RsbW2, determines the functionality of RsfB as an anti-sigma antagonist. Furthermore, RsfB was identified as the major anti-σ F antagonist in M. smegmatis ( Oh et al., 2020 ).…”

Section: Canonical Stas Domain Only Proteinsmentioning

confidence: 99%

STAS Domain Only Proteins in Bacterial Gene Regulation

Moy

Seshu

2021

Front. Cell. Infect. Microbiol.

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Sulfate Transport Anti-Sigma antagonist domains (Pfam01740) are found in all branches of life, from eubacteria to mammals, as a conserved fold encoded by highly divergent amino acid sequences. These domains are present as part of larger SLC26/SulP anion transporters, where the STAS domain is associated with transmembrane anchoring of the larger multidomain protein. Here, we focus on STAS Domain only Proteins (SDoPs) in eubacteria, initially described as part of the Bacillus subtilisRegulation of Sigma B (RSB) regulatory system. Since their description in B. subtilis, SDoPs have been described to be involved in the regulation of sigma factors, through partner-switching mechanisms in various bacteria such as: Mycobacterium. tuberculosis, Listeria. monocytogenes, Vibrio. fischeri, Bordetella bronchiseptica, among others. In addition to playing a canonical role in partner-switching with an anti-sigma factor to affect the availability of a sigma factor, several eubacterial SDoPs show additional regulatory roles compared to the original RSB system of B. subtilis. This is of great interest as these proteins are highly conserved, and often involved in altering gene expression in response to changes in environmental conditions. For many of the bacteria we will examine in this review, the ability to sense environmental changes and alter gene expression accordingly is critical for survival and colonization of susceptible hosts.

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“…In our ND-induced system transition to the differentially culturable state did not require activation of the DosR regulon, but involved two alternative sigma factors, SigH and SigF and their regulons, previously implicated in adaptation to redox stress and respiration-inhibitory conditions [36,37,61]. Overall, the transcriptomic signature of ND-treated DCB was associated with inhibition of cell division, repair of NO-induced damage, metabolic reprogramming to restore redox balance and membrane potential (Figure 6).…”

Section: Discussionmentioning

confidence: 68%

Exposure to nitric oxide drives transition to differential culturability inMycobacterium tuberculosis

Glenn

Gap-Gaupool

Waddell

et al. 2021

Preprint

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Rationale: Mycobacterium tuberculosis (Mtb) has a devastating impact on global health. Mtb is the causative agent of human pulmonary tuberculosis (TB), which claims 1.4 million lives per annum. During infection, differentially culturable bacilli (DCB) that fail to produce colonies on solid media but grow in liquid media supplemented with resuscitation-promoting factor (Rpf) proteins are formed. These Rpf-dependent mycobacteria are a major barrier to developing improved TB treatments and diagnostic tools. Objectives: To evaluate whether exposure to nitric oxide (NO), a prominent host defense molecule, drives the generation of Rpf-dependent DCB. Methods: A new NO donor (ND) for sustained NO release was synthesized. Growth assays, flow cytometry analysis, and global transcriptional profiling, were used to characterize ND-treated Mtb and Mycobacterium bovis BCG in vitro. Mycobacterial DCB phenotypes were also investigated after infection of THP-1 human cells, which were activated with retinoic acid and vitamin D3. Measurements and Main Results: DCB were generated after exposure to ND and during infection of activated THP-1 cells. Resuscitation of these DCB was severely impaired by a specific Rpf inhibitor (3-nitro-4-thiocyanato-phenyl)-phenyl-methanone. Global transcriptomic analyses revealed the down-regulation of three (rpfA, rpfB and rpfE) of the five genes coding for Rpf proteins. Conclusion: A new model for investigation of the transition of Mtb into an Rpf-dependent differentially culturable state is presented. The system reveals mechanistic insights into the generation of Rpf-dependent Mtb during TB disease and demonstrates the role of NO in this process.

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The Partner Switching System of the SigF Sigma Factor in Mycobacterium smegmatis and Induction of the SigF Regulon Under Respiration-Inhibitory Conditions

Cited by 11 publications

References 61 publications

Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis

Cobalamin is present in cells of non-tuberculous mycobacteria, but not in Mycobacterium tuberculosis

STAS Domain Only Proteins in Bacterial Gene Regulation

Exposure to nitric oxide drives transition to differential culturability inMycobacterium tuberculosis

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