Bacterial alarmone (p)ppGpp, is a global regulator responsible for the stringent control. Two homologous (p)ppGpp synthetases, RelA and SpoT, have been identified and characterized in Escherichia coli, whereas Gram-positive bacteria such as Bacillus subtilis have been thought to possess only a single RelA-SpoT enzyme. We have now identified two genes, yjbM and ywaC, in B. subtilis that encode a novel type of alarmone synthetase. The predicted products of these genes are relatively small proteins ( approximately 25 kDa) that correspond to the (p)ppGpp synthetase domain of RelA-SpoT family members. A database survey revealed that genes homologous to yjbM and ywaC are conserved in certain bacteria belonging to Firmicutes or Actinobacteria phyla but not in other phyla such as Proteobacteria. We designated the proteins as small alarmone synthetases (SASs) to distinguish them from RelA-SpoT proteins. The (p)ppGpp synthetase function of YjbM and YwaC was confirmed by genetic complementation analysis and by in vitro assay of enzyme activity. Molecular genetic analysis also revealed that ywaC is induced by alkaline shock, resulting in the transient accumulation of ppGpp. The SAS proteins thus likely function in the biosynthesis of alarmone with a mode of action distinct from that of RelA-SpoT homologues.
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http://dx.doi.org/10.1111/j.1365-2958.2007.06018.x | DOI Listing |
Int J Biol Macromol
January 2025
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University; Yangling, Shaanxi 712100, China. Electronic address:
Biofilms are complex adhesive structures that establish chronic infection and allow robust protection from external stressors such as antibiotics. Cellulose as one of the compositions of bacteria biofilm which protect bacteria from stress, host immune responses and resistance to antibiotics. Bacterial stress responses are regulated via guanosine pentaphosphate and tetraphosphate (p)ppGpp.
View Article and Find Full Text PDFPersisters describe phenotypically switched cells refractory to antibiotic killing in a genetically susceptible population, while preserving the ability to resume growth when antibiotics are discontinued1,2. Since its proposal 70 years ago, great strides were made to build the framework regarding persistence, including defining triggered, spontaneous and antibiotic-induced persisters. However, challenges remain in characterizing the molecular determinants underlying the phenotypic switch into persistence3.
View Article and Find Full Text PDFMol Microbiol
December 2024
Center for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Fluidity is an inherent property of biological membranes and its maintenance (homeoviscous adaptation) is important for optimal functioning of membrane-associated processes. The fluidity of bacterial cytoplasmic membrane increases with temperature or an increase in the proportion of unsaturated fatty acids and vice versa. We found that strains deficient in the synthesis of guanine nucleotide analogs (p)ppGpp and lacking FadR, a transcription factor involved in fatty acid metabolism exhibited a growth defect that was rescued by an increase in growth temperature or unsaturated fatty acid content.
View Article and Find Full Text PDFmBio
November 2024
Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Gene expression and proper downstream cellular functions upon facing environmental shifts depend on the combined and cooperative regulation of genetic networks. Here, we identified cAMP receptor protein (CRP) as a master regulator of (p)ppGpp (guanosine tetra- and penta-phosphate) homeostasis. Via CRP-mediated direct transcriptional regulation of the (p)ppGpp synthetase/hydrolase RelA and SpoT, cAMP-CRP stimulates pervasive accumulation of (p)ppGpp under glucose-limiting conditions.
View Article and Find Full Text PDFFront Microbiol
August 2024
Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
In this study, we demonstrated that both the expression of most ribosomal protein genes and the amount of ribosomes were decreased in the Δ mutant of , in which the major terminal oxidase ( cytochrome oxidase) of the respiratory electron transport chain (ETC) is inactivated, compared to those in the wild-type strain. Deletion of the gene encoding the major (p)ppGpp synthetase in the background of the Δ mutant restored the reduced expression of ribosomal protein genes, suggesting that inhibition of the respiratory ETC leads to the Rel-dependent stringent response (SR) in this bacterium. Both a decrease in the expression of ribosomal protein genes by overexpression of and the increased expression of in the Δ mutant relative to the wild-type strain support the Rel-dependent induction of SR in the Δ mutant.
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