Roles and regulation of Spx family transcription factors in Bacillus subtilis and related species

Rojas‐Tapias, Daniel F.; Helmann, John D.

doi:10.1016/bs.ampbs.2019.05.003

Cited by 26 publications

(25 citation statements)

References 106 publications

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“…Spx, initially named as s uppressor of clp P and clp X , is highly conserved among low GC-content Gram-positive bacteria and is widely distributed in the phylum Firmicutes, including some disseminated human pathogens ( 23 , 24 ). Genetic and biochemical studies have shown that B. subtilis Spx is a pleiotropic transcriptional regulator that responds to various stresses (such as oxidative stress, thermo damage, and cell wall-active antibiotics) and serves as a prototype for a large group of stress-response regulators ( 25–29 ).…”

Section: Introductionmentioning

confidence: 99%

Structural basis of transcription activation by the global regulator Spx

Shi

Wen

et al. 2021

Nucleic Acids Research

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Spx is a global transcriptional regulator in Gram-positive bacteria and has been inferred to efficiently activate transcription upon oxidative stress by engaging RNA polymerase (RNAP) and promoter DNA. However, the precise mechanism by which it interacts with RNAP and promoter DNA to initiate transcription remains obscure. Here, we report the cryo-EM structure of an intact Spx-dependent transcription activation complex (Spx–TAC) from Bacillus subtilis at 4.2 Å resolution. The structure traps Spx in an active conformation and defines key interactions accounting for Spx-dependent transcription activation. Strikingly, an oxidized Spx monomer engages RNAP by simultaneously interacting with the C-terminal domain of RNAP alpha subunit (αCTD) and σA. The interface between Spx and αCTD is distinct from those previously reported activators, indicating αCTD as a multiple target for the interaction between RNAP and various transcription activators. Notably, Spx specifically wraps the conserved –44 element of promoter DNA, thereby stabilizing Spx–TAC. Besides, Spx interacts extensively with σA through three different interfaces and promotes Spx-dependent transcription activation. Together, our structural and biochemical results provide a novel mechanistic framework for the regulation of bacterial transcription activation and shed new light on the physiological roles of the global Spx-family transcription factors.

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Section: Introductionmentioning

confidence: 99%

Structural basis of transcription activation by the global regulator Spx

Shi

Wen

et al. 2021

Nucleic Acids Research

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“…The strongest downregulation is that of Spx transcription factor and, while not unique to 8-1, it is more than five times stronger in this strain than in Ym1 (20.62- vs. 3.8-fold). The Spx transcription factors usually interact directly with the RNA polymerase and are mostly involved in oxidative stress; several species of LAB have been reported to contain from two to seven Spx paralogs [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

Butanol Tolerance of Lactiplantibacillus plantarum: A Transcriptome Study

Petrov

Arsov

Petrova

2021

Genes

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Biobutanol is a promising alternative fuel with impaired microbial production thanks to its toxicity. Lactiplantibacillus plantarum (L. plantarum) is among the few bacterial species that can naturally tolerate 3% (v/v) butanol. This study aims to identify the genetic factors involved in the butanol stress response of L. plantarum by comparing the differential gene expression in two strains with very different butanol tolerance: the highly resistant Ym1, and the relatively sensitive 8-1. During butanol stress, a total of 319 differentially expressed genes (DEGs) were found in Ym1, and 516 in 8-1. Fifty genes were upregulated and 54 were downregulated in both strains, revealing the common species-specific effects of butanol stress: upregulation of multidrug efflux transporters (SMR, MSF), toxin-antitoxin system, transcriptional regulators (TetR/AcrR, Crp/Fnr, and DeoR/GlpR), Hsp20, and genes involved in polysaccharide biosynthesis. Strong inhibition of the pyrimidine biosynthesis occurred in both strains. However, the strains differed greatly in DEGs responsible for the membrane transport, tryptophan synthesis, glycerol metabolism, tRNAs, and some important transcriptional regulators (Spx, LacI). Uniquely upregulated in the butanol-resistant strain Ym1 were the genes encoding GntR, GroEL, GroES, and foldase PrsA. The phosphoenolpyruvate flux and the phosphotransferase system (PTS) also appear to be major factors in butanol tolerance.

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“…Proteins in bold were further studied. Identified Proteins cellular process BrxB [ 3 ] bacilliredoxin BdhA [ 3 ] acetoine/butanediol dehydrogenase SalA [ 1 ] control of alkaline protease expression PyrH [ 1 ] pyrimidine biosynthesis PyrAA [ 6 ] pyrimidine biosynthesis PyrAB [ 8 ] pyrimidine biosynthesis PyrG [ 7 ] pyrimidine biosynthesis PyrE [ 4 ] pyrimidine biosynthesis GapB [ 4 ] glycolysis PfkA [ 3 ] glycolysis YtsJ [ 3 ] NADP-dependent malate dehydrogenase SucC [ 4 ] tricarboxylic acid cycle Bdr (YpdA) [ 3 ] oxidoreductase activity FolD [ 3 ] formylation of Met-tRNA(fMet) AbrB [ 1 ] transition state regulator TufA [ 2 ] elongation factor Tu (translation) RpsB [ 1 ] translation GatA [ 3 ] ...…”

Section: Resultsmentioning

confidence: 99%

“…Cells contain several systems to maintain cysteine residues and other thiols in their reduced form in the cytosol, and dedicated pathways for the controlled oxidation of cysteines to form disulfide bonds in secreted and periplasmic proteins. Maintaining the redox balance of cellular thiols is critical for cell physiology, and oxidation can lead to a specific type of oxidative stress known as disulfide stress [ [1] , [2] , [3] , [4] ]. Reduction of intracellular thiols ultimately relies on the reducing power of NADPH, which serves as a cofactor to reduce thiol groups in either protein-based thiol reductants like thioredoxin (Trx) or low molecular weight (LMW) thiols.…”

Section: Introductionmentioning

confidence: 99%

The Bacillus subtilis monothiol bacilliredoxin BrxC (YtxJ) and the Bdr (YpdA) disulfide reductase reduce S-bacillithiolated proteins

Gaballa

Helmann

2021

Redox Biology

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The bacterial cytosol is generally a reducing environment with protein cysteine residues maintained in their thiol form. The low molecular weight thiol bacillithiol (BSH) serves as a general thiol reductant, analogous to glutathione, in a wide range of bacterial species. Proteins modified by disulfide bond formation with BSH ( S -bacillithiolation) are reduced by the action of bacilliredoxins, BrxA and BrxB. Here, the YtxJ protein is identified as a monothiol bacilliredoxin, renamed BrxC, and is implicated in BSH removal from oxidized cytosolic proteins, including the glyceraldehyde 3-phosphate dehydrogenases GapA and GapB. BrxC can also debacillithiolate the mixed disulfide form of the bacilliredoxin BrxB. Bdr is a thioredoxin reductase-like flavoprotein with bacillithiol-disulfide (BSSB) reductase activity. Here, Bdr is shown to additionally function as a bacilliredoxin reductase. Bdr and BrxB function cooperatively to debacillithiolate OhrR, a transcription factor regulated by S -bacillithiolation on its sole cysteine residue. Collectively, these results expand our understanding of the BSH redox network comprised of three bacilliredoxins and a BSSB reductase that serve to counter the widespread protein S -bacillithiolation that results from conditions of disulfide stress.

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Roles and regulation of Spx family transcription factors in Bacillus subtilis and related species

Cited by 26 publications

References 106 publications

Structural basis of transcription activation by the global regulator Spx

Structural basis of transcription activation by the global regulator Spx

Butanol Tolerance of Lactiplantibacillus plantarum: A Transcriptome Study

The Bacillus subtilis monothiol bacilliredoxin BrxC (YtxJ) and the Bdr (YpdA) disulfide reductase reduce S-bacillithiolated proteins

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