An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp
Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors1. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the...
| Principais autores: | , , , , , , , , , |
|---|---|
| Outros Autores: | |
| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Springer Science and Business Media LLC
2020
|
| Acesso em linha: | https://hdl.handle.net/1721.1/125211 |
| _version_ | 1826201677388054528 |
|---|---|
| author | Ahmad, Shehryar Wang, Boyuan Walker, Matthew D. Tran, Hiu-Ki R. Stogios, Peter J. Savchenko, Alexei Grant, Robert A McArthur, Andrew G. Laub, Michael T Whitney, John C. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ahmad, Shehryar Wang, Boyuan Walker, Matthew D. Tran, Hiu-Ki R. Stogios, Peter J. Savchenko, Alexei Grant, Robert A McArthur, Andrew G. Laub, Michael T Whitney, John C. |
| author_sort | Ahmad, Shehryar |
| collection | MIT |
| description | Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors1. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown2. Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress3. However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria. |
| first_indexed | 2024-09-23T11:55:05Z |
| format | Article |
| id | mit-1721.1/125211 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:55:05Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1252112022-10-01T06:58:40Z An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp Ahmad, Shehryar Wang, Boyuan Walker, Matthew D. Tran, Hiu-Ki R. Stogios, Peter J. Savchenko, Alexei Grant, Robert A McArthur, Andrew G. Laub, Michael T Whitney, John C. Massachusetts Institute of Technology. Department of Biology Bacteria have evolved sophisticated mechanisms to inhibit the growth of competitors1. One such mechanism involves type VI secretion systems, which bacteria can use to inject antibacterial toxins directly into neighbouring cells. Many of these toxins target the integrity of the cell envelope, but the full range of growth inhibitory mechanisms remains unknown2. Here we identify a type VI secretion effector, Tas1, in the opportunistic pathogen Pseudomonas aeruginosa. The crystal structure of Tas1 shows that it is similar to enzymes that synthesize (p)ppGpp, a broadly conserved signalling molecule in bacteria that modulates cell growth rate, particularly in response to nutritional stress3. However, Tas1 does not synthesize (p)ppGpp; instead, it pyrophosphorylates adenosine nucleotides to produce (p)ppApp at rates of nearly 180,000 molecules per minute. Consequently, the delivery of Tas1 into competitor cells drives rapid accumulation of (p)ppApp, depletion of ATP, and widespread dysregulation of essential metabolic pathways, thereby resulting in target cell death. Our findings reveal a previously undescribed mechanism for interbacterial antagonism and demonstrate a physiological role for the metabolite (p)ppApp in bacteria. National Institutes of Health (Grant R01-GM082899) 2020-05-13T15:51:00Z 2020-05-13T15:51:00Z 2019-11 2019-05 2020-05-11T15:56:29Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 https://hdl.handle.net/1721.1/125211 Ahmad, Shehryar et al. "An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp." Nature 575, 7784 (November 2019): 674–678 © 2019 The Author(s) en http://dx.doi.org/10.1038/s41586-019-1735-9 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Ahmad, Shehryar Wang, Boyuan Walker, Matthew D. Tran, Hiu-Ki R. Stogios, Peter J. Savchenko, Alexei Grant, Robert A McArthur, Andrew G. Laub, Michael T Whitney, John C. An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title | An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title_full | An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title_fullStr | An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title_full_unstemmed | An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title_short | An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp |
| title_sort | interbacterial toxin inhibits target cell growth by synthesizing p ppapp |
| url | https://hdl.handle.net/1721.1/125211 |
| work_keys_str_mv | AT ahmadshehryar aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT wangboyuan aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT walkermatthewd aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT tranhiukir aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT stogiospeterj aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT savchenkoalexei aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT grantroberta aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT mcarthurandrewg aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT laubmichaelt aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT whitneyjohnc aninterbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT ahmadshehryar interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT wangboyuan interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT walkermatthewd interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT tranhiukir interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT stogiospeterj interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT savchenkoalexei interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT grantroberta interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT mcarthurandrewg interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT laubmichaelt interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp AT whitneyjohnc interbacterialtoxininhibitstargetcellgrowthbysynthesizingpppapp |