(p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms
Abstract (p)ppGpp is the master regulator of bacterial stress responses, orchestrating cellular physiology via the stringent response to promote survival and adaptation. In response to nutritional challenges and stress, (p)ppGpp extensively rewires the transcriptome. Here, we demonstrate that (p)ppG...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-025-00795-7 |
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| author | Florian Engelhardt Kathryn Turnbull Melisa Gür Mathias Müsken Matthias Preusse Susanne Häussler Mohammad Roghanian |
| author_facet | Florian Engelhardt Kathryn Turnbull Melisa Gür Mathias Müsken Matthias Preusse Susanne Häussler Mohammad Roghanian |
| author_sort | Florian Engelhardt |
| collection | DOAJ |
| description | Abstract (p)ppGpp is the master regulator of bacterial stress responses, orchestrating cellular physiology via the stringent response to promote survival and adaptation. In response to nutritional challenges and stress, (p)ppGpp extensively rewires the transcriptome. Here, we demonstrate that (p)ppGpp production in Pseudomonas aeruginosa is gradual and relative to stress severity, rather than binary (on/off). Transcriptomic analysis reveals that (p)ppGpp ensures proportionate cellular responses to stress by imposing a layer-by-layer regulation of gene expression. These effects intensify as (p)ppGpp levels rise, with up to a quarter of the genome differentially regulated at maximal levels. Initial increases in (p)ppGpp reduce growth and metabolism while suppressing motility and pyocyanin production. At higher levels, biofilm-related genes are upregulated at the expense of virulence genes, promoting the formation of condensed biofilms. Finally, (p)ppGpp-driven reprogramming induces antimicrobial tolerance, particularly under biofilm conditions, independently of its effects on growth. |
| format | Article |
| id | doaj-art-7b2ac257bb1f4854ad3ba8d747f4fe90 |
| institution | Kabale University |
| issn | 2055-5008 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj-art-7b2ac257bb1f4854ad3ba8d747f4fe902025-08-20T03:42:40ZengNature Portfolionpj Biofilms and Microbiomes2055-50082025-08-0111111410.1038/s41522-025-00795-7(p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilmsFlorian Engelhardt0Kathryn Turnbull1Melisa Gür2Mathias Müsken3Matthias Preusse4Susanne Häussler5Mohammad Roghanian6Department of Molecular Bacteriology, Helmholtz Centre for Infection ResearchDepartment of Clinical Microbiology, RigshospitaletInstitute for Molecular Bacteriology, Twincore, Centre for Clinical and Experimental Infection ResearchCentral Facility for Microscopy, Helmholtz Centre for Infection ResearchDepartment of Molecular Bacteriology, Helmholtz Centre for Infection ResearchDepartment of Molecular Bacteriology, Helmholtz Centre for Infection ResearchDepartment of Clinical Microbiology, RigshospitaletAbstract (p)ppGpp is the master regulator of bacterial stress responses, orchestrating cellular physiology via the stringent response to promote survival and adaptation. In response to nutritional challenges and stress, (p)ppGpp extensively rewires the transcriptome. Here, we demonstrate that (p)ppGpp production in Pseudomonas aeruginosa is gradual and relative to stress severity, rather than binary (on/off). Transcriptomic analysis reveals that (p)ppGpp ensures proportionate cellular responses to stress by imposing a layer-by-layer regulation of gene expression. These effects intensify as (p)ppGpp levels rise, with up to a quarter of the genome differentially regulated at maximal levels. Initial increases in (p)ppGpp reduce growth and metabolism while suppressing motility and pyocyanin production. At higher levels, biofilm-related genes are upregulated at the expense of virulence genes, promoting the formation of condensed biofilms. Finally, (p)ppGpp-driven reprogramming induces antimicrobial tolerance, particularly under biofilm conditions, independently of its effects on growth.https://doi.org/10.1038/s41522-025-00795-7 |
| spellingShingle | Florian Engelhardt Kathryn Turnbull Melisa Gür Mathias Müsken Matthias Preusse Susanne Häussler Mohammad Roghanian (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms npj Biofilms and Microbiomes |
| title | (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| title_full | (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| title_fullStr | (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| title_full_unstemmed | (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| title_short | (p)ppGpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| title_sort | p ppgpp imposes graded transcriptional changes to impair motility and promote antibiotic tolerance in biofilms |
| url | https://doi.org/10.1038/s41522-025-00795-7 |
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