Genome-directed study reveals the diversity of Salmonella T6SS effectors and identifies a novel family of lipid-targeting antibacterial toxins
Open accessPreprint — published as 10.1371/journal.pbio.3003680 · Paper page
Abstract
Bacterial warfare is a common and ancient phenomenon in nature, where bacterial species use strategies to inhibit the growth or kill competitors. This involves the production and deployment of antibacterial toxins that disrupt essential cellular processes in target cells. The continuous arms race in which bacteria acquire new toxin and immunity proteins to promote increased adaptation to their environment is responsible for the diversification of this toxin repertoire. Here, we deployed in-silico strategies to analyze 10,000 genomes and identify effectors secreted via the type VI secretion system of Salmonella . We identified 128 candidates, which are widespread in a vast array of Salmonella serovars and other bacterial species. Tox-Act1 is among the most frequent candidates and was selected for in-depth characterization. Tox-Act1 contains a permuted NlpC/P60 papain-like catalytic core characteristic of lipid-targeting members rather than the typical peptidases or amidases. Evolutionary analysis revealed the relationship of Tox-Act1 with acyltransferases. Biochemical assays with purified toxin and lipidomics of intoxicated cells showed that Tox-Act1 exhibits phospholipase activity, cleaving off acyl groups from phosphatidylglycerol and phosphatidylethanolamine. In addition, we demonstrate that Tox-Act1 is secreted in a T6SS-dependent manner and provide a competitive advantage during colonization of the gut of infected mice. This work broadens our understanding of toxin domains and provides the first direct characterization of a lipid-targeting NlpC/P60 domain in biological conflicts.
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Blondel, C., Amaya, F. A., Reyes-Méndez, F., Soriano-Mora, V., Vargas, C., Parra, A., Opazo, M. C., Toledo, V., Barros-Infante, M. F., Santiviago, C. A., et al. (2025) · Journal of Bacteriology · doi:10.1128/jb.00188-25 · Cited by 11
“This analysis resulted in the identification of more than a hundred candidate effector proteins carrying toxin domains with potential antibacterial activity, considerably expanding our knowledge on the diversity of T6SS effectors (26).”
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- Authors
- Nicastro, G. G., Sibinelli-Sousa, S., Hespanhol, J. T., Santos, T. W. C., Munoz, J. P., Santos, R. S., Perez-Sepulveda, B. M., Miyamoto, S., Aravind, L., de Souza, R. F., & Bayer-Santos, E.
- Affiliations
- National Institutes of Health (US)
- The University of Texas at Austin (US)
- Universidade de São Paulo (BR)
- University of Liverpool (GB)
- ORCID
- Venue
- PLoS Biology
- Publisher
- openRxiv
- Published
- 2024-09-28
- Volume
- 24
- Issue
- 3
- Pages
- e3003680-e3003680
- ISSN
- 1544-9173 (ISSN-L)
- PMC
- PMC11996579
- OpenAlex
- W7137868969
- Cited by
- 9
- References
- 49
- Citations by year
- 2026: 6 · 2025: 3
- FWCI
- 18.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Energy (DE-SC 0014664, SC0014664)
- Oak Ridge Associated Universities
- University of Texas at Austin
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2017-02178-2, 21/10577-0, 2013/079378, 88887, 2021/, 2013/07937, 16/09047-8, 13/07937-8)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (2016/09047-8, 88887, 2023-00, 2021/10577-0, 88887.823029/2023-00, 2013/07937-8)
- Governo Brasil
- National Institutes of Health (LM594244)
- Oak Ridge Institute for Science and Education (DE–SC0014664, SC0014664)
- College of Natural Sciences, University of Texas at Austin
- Division of Graduate Education
- U.S. National Library of Medicine (DE-SC0014664, ZIALM594244)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Keywords
- Salmonella, type VI secretion system, T6SS effectors, phospholipase activity, phosphatidylglycerol, phosphatidylethanolamine, bacterial toxins, immunity genes, acyltransferase, intestinal colonization, bacterial competition
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