Characterisation of Bacillus subtilis Transcriptional Regulators Involved in Metabolic Processes

Brantl, Sabine; Licht, Andreas

doi:10.2174/138920310791233396

Cited by 6 publications

(3 citation statements)

References 85 publications

(134 reference statements)

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“…Amino acids are essential for synthesis of proteins and other macromolecules, and many can also be catabolized to yield intermediates of the tricarboxylic acid (TCA) cycle. Amino acid metabolism is governed by master regulators, such as CcpA, TnrA and CodY, working in concert with pathway‐specific regulation by transcriptional, translational and post‐translational mechanisms in a complex, interlinked network (Sonenshein, ; Brantl and Licht, ; Geiger and Wolz, ).…”

Section: Introductionmentioning

confidence: 99%

Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis

Zhao

Roistacher

Helmann

2018

Molecular Microbiology

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Peptidoglycan synthesis is an important target for antibiotics and relies on intermediates derived from central metabolism. As a result, alterations of metabolism may affect antibiotic sensitivity. An aspB mutant is auxotrophic for aspartate (Asp) and asparagine (Asn) and lyses when grown in Difco sporulation medium (DSM), but not in LB medium. Genetic and physiological studies, supported by amino acid analysis, reveal that cell lysis in DSM results from Asp limitation due to a relatively low Asp and high glutamate (Glu) concentrations, with Glu functioning as a competitive inhibitor of Asp uptake by the major Glu/Asp transporter GltT. Lysis can be specifically suppressed by supplementation with 2,6-diaminopimelate (DAP), which is imported by two different cystine uptake systems. These studies suggest that aspartate limitation depletes the peptidoglycan precursor meso-2,6-diaminopimelate (mDAP), inhibits peptidoglycan synthesis, upregulates the cell envelope stress response mediated by σ and eventually leads to cell lysis. Aspartate limitation sensitizes cells to antibiotics targeting late steps of PG synthesis, but not steps prior to the addition of mDAP into the pentapeptide sidechain. This work highlights the ability of perturbations of central metabolism to sensitize cells to peptidoglycan synthesis inhibitors.

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Section: Introductionmentioning

confidence: 99%

Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis

Zhao

Roistacher

Helmann

2018

Molecular Microbiology

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“…The activity of RNAP has to be tightly regulated. This is mediated by various factors, such as small molecules including nucleoside triphosphates (NTPs) and ppGpp , by small RNAs, like 6S and Ms1 RNA , and by numerous proteins .…”

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confidence: 99%

Domain structure of HelD, an interaction partner of Bacillus subtilis RNA polymerase

et al. 2019

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The HelD is a helicase‐like protein binding to Bacillus subtilis RNA polymerase (RNAP), stimulating transcription in an ATP‐dependent manner. Here, our small angle X‐ray scattering data bring the first insights into the HelD structure: HelD is compact in shape and undergoes a conformational change upon substrate analog binding. Furthermore, the HelD domain structure is delineated, and a partial model of HelD is presented. In addition, the unique N‐terminal domain of HelD is characterized as essential for its transcription‐related function but not for ATPase activity, DNA binding, or binding to RNAP. The study provides a topological basis for further studies of the role of HelD in transcription.

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“…Bacillus subtilis produces a group of eight extracellular proteases (Schonbichler et al, 2020 ), which mediate the extracellular degradation of proteins (Harwood & Kikuchi, 2022 ) and have been postulated to be a public good required to support growth (Gray et al, 2019 ). Transcriptional regulation of extracellular protease production is intricate and largely tied to nutrient stress via CodY (Brantl & Licht, 2010 ) and entry into stationary phase via the response regulator DegU (Murray et al, 2009 ). Significant heterogeneity of transcription of at least some of the extracellular protease coding regions in isogenic populations is apparent (Veening et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Bacillus subtilis extracellular protease production incurs a context‐dependent cost

Rosazza

Eigentler

Earl

et al. 2023

Molecular Microbiology

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Microbes encounter a wide range of polymeric nutrient sources in various environmental settings, which require processing to facilitate growth. Bacillus subtilis, a bacterium found in the rhizosphere and broader soil environment, is highly adaptable and resilient due to its ability to utilise diverse sources of carbon and nitrogen. Here, we explore the role of extracellular proteases in supporting growth and assess the cost associated with their production. We provide evidence of the essentiality of extracellular proteases when B. subtilis is provided with an abundant, but polymeric nutrient source and demonstrate the extracellular proteases as a shared public good that can operate over a distance. We show that B. subtilis is subjected to a public good dilemma, specifically in the context of growth sustained by the digestion of a polymeric food source. Furthermore, using mathematical simulations, we uncover that this selectively enforced dilemma is driven by the relative cost of producing the public good. Collectively, our findings reveal how bacteria can survive in environments that vary in terms of immediate nutrient accessibility and the consequent impact on the population composition. These findings enhance our fundamental understanding of how bacteria respond to diverse environments, which has importance to contexts ranging from survival in the soil to infection and pathogenesis scenarios.

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Characterisation of Bacillus subtilis Transcriptional Regulators Involved in Metabolic Processes

Cited by 6 publications

References 85 publications

Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis

Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis

Domain structure of HelD, an interaction partner of Bacillus subtilis RNA polymerase

Bacillus subtilis extracellular protease production incurs a context‐dependent cost

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