Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Internal expression of Rhs toxins allows protection against Rhs toxin delivery by stabilizing the cognate Rhs antitoxins
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Show others and affiliations
2022 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Rhs elements are some of the most positively selected genes known and were recently found to function as type II TA-systems in addition to their previous role as delivered toxins. Antitoxins of type II TA systems are often inherently unstable proteins. Here we discover that the RhsI immunity proteins in Salmonella enterica serovar Typhimurium are also unstable on their own, but stabilized in the presence of their cognate toxins. This raises interesting questions regarding how such unstable immunity proteins can protect against incoming toxins delivered by neighboring attackers. In this study, we observed that one Rhs immunity protein can protect against more than one toxin. Therefore, the internal expression of RhsCT-I could be important for protection against delivered Rhs toxins in addition to regulating Salmonellagrowth in macrophages. The internal transcripts of rhsCT-I are upregulated in InSPI-2 and within macrophages by the combined action of RpoS, PhoP/Q and H-NS. These are the same regulators that control the expression of the type 6 secretion system known to deliver Rhs effectors in Salmonella. This suggests that expression of rhsCT-I is elevated under conditions that favor delivery, which further supports a role for the internal expression of Rhs proteins in protection against toxin delivery. 

Place, publisher, year, edition, pages
2022.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-487780OAI: oai:DiVA.org:uu-487780DiVA, id: diva2:1707908
Available from: 2022-11-02 Created: 2022-11-02 Last updated: 2022-11-11
In thesis
1. To defend or to offend?: Bacterial defence and competition systems
Open this publication in new window or tab >>To defend or to offend?: Bacterial defence and competition systems
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacteria are prokaryotic microorganisms that can be found in all niches of the biosphere. Bacteria must constantly evolve in order to survive and adapt to their environments. Defence systems and competition systems play a vital role in ensuring the survival of bacteria. The projects included in this thesis aim to further understand how these systems function, as well as adapting them in order to design probiotic strains with built-in biocontainment mechanisms. In paper I, we investigate how internal expression of Rearrangement hotspot (Rhs) toxins allows protection against Rhs toxin delivery in S. Typhimurium. In paper II, we examine bacterial competition systems found in enterotoxigenic E. coli (ETEC) strains and explore the evolution of toxin arsenals within ETEC family lineages. In paper III, we develop a fluorescence flow cytometry-based high-throughput screening method and apply it to isolate a highly competitive commensal E. coli strain that possesses a diverse arsenal of competition systems. In paper IV, we design and construct a synthetic CRISPR system that is able to protect E. coli from acquisition of antibiotic resistance genes through horizontal gene transfer. The work presented in this thesis contribute to our understanding of the functions of bacterial defence and competition systems, at the same time, laying the groundwork for how these systems can be studied in a high-throughput manner as well as how they can be adapted in the future to design synthetic microbial strains with clinical and environmental applications.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2022. p. 31
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2217
Keywords
bacterial defence systems; bacterial competition systems; toxin-antitoxin systems; colicin; contact-dependent growth inhibition (CDI); type VI secretion system (T6SS); Rearrangement hotspot (Rhs) proteins; CRISPR; horizontal gene transfer; antibiotic resistance; Salmonella; Enterotoxigenic E. coli (ETEC); probiotics; synthetic biology.
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-487784 (URN)978-91-513-1657-4 (ISBN)
Public defence
2022-12-20, Room A1:107, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2022-11-28 Created: 2022-11-02 Last updated: 2022-11-28

Open Access in DiVA

No full text in DiVA

By organisation
Department of Cell and Molecular BiologyScience for Life Laboratory, SciLifeLab
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 182 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf