ArticleNature communications2019
Multisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Phosphorylation of a conserved intrinsically disordered region is necessary for activation of a bacterial Hanks-type Ser/Thr kinase signaling pathway.bioRxiv : the preprint server for biology · 2025Article
- A shared alarmone-GTP switch controls persister formation in bacteria.Nature microbiology · 2025Article
- Bacteriophage-driven microbial phenotypic heterogeneity: ecological and biogeochemical importance.NPJ biofilms and microbiomes · 2025Review
- An atlas of bacterial serine-threonine kinases reveals functional diversity and key distinctions from eukaryotic kinases.Science signaling · 2025Article
- Priestia megaterium cells are primed for surviving lethal doses of antibiotics and chemical stress.Communications biology · 2025Article
- Gram-positive bacteria are primed for surviving lethal doses of antibiotics and chemical stress.bioRxiv : the preprint server for biology · 2024Article
- Article
- Giving a signal: how protein phosphorylation helps Bacillus navigate through different life stages.FEMS microbiology reviews · 2023Review
- Growth rate is modulated by monitoring cell wall precursors in Bacillus subtilis.Nature microbiology · 2023Article
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation.PLoS genetics · 2022Article
- Many birds with one stone: targeting the (p)ppGpp signaling pathway of bacteria to improve antimicrobial therapy.Biophysical reviews · 2021Review
- Comparative Phenotypic, Proteomic, and Phosphoproteomic Analysis Reveals Different Roles of Serine/Threonine Phosphatase and Kinase in the Growth, Cell Division, and Pathogenicity ofMicroorganisms · 2021Article
- Modular and Single-Cell Sensors of Bacterial Ser/Thr Kinase Activity.ACS synthetic biology · 2021Article
- Tunable phenotypic variability through an autoregulatory alternative sigma factor circuit.Molecular systems biology · 2021Article
- Article
- Association of mprF mutations with cross-resistance to daptomycin and vancomycin in methicillin-resistant Staphylococcus aureus (MRSA).Scientific reports · 2020Article
- (p)ppGpp and Its Role in Bacterial Persistence: New Challenges.Antimicrobial agents and chemotherapy · 2020Review
- Exoproteomics for Better UnderstandingToxins · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Isogenic populations of cells exhibit phenotypic variability that has specific physiological consequences. Individual bacteria within a population can differ in antibiotic tolerance, but whether this variability can be regulated or is generally an unavoidable consequence of stochastic fluctuations is unclear. Here we report that a gene encoding a bacterial (p)ppGpp synthetase in Bacillus subtilis, sasA, exhibits high levels of extrinsic noise in expression. We find that sasA is regulated by multisite phosphorylation of the transcription factor WalR, mediated by a Ser/Thr kinase-phosphatase pair PrkC/PrpC, and a Histidine kinase WalK of a two-component system. This regulatory intersection is crucial for controlling the appearance of outliers; rare cells with unusually high levels of sasA expression, having increased antibiotic tolerance. We create a predictive model demonstrating that the probability of a given cell surviving antibiotic treatment increases with sasA expression. Therefore, multisite phosphorylation can be used to strongly regulate variability in antibiotic tolerance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.