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Thesis
Defense against bacterial toxin secretion systems
University of Iowa
Master of Science (MS), University of Iowa
Autumn 2023
DOI: 10.25820/etd.006929
Abstract
The human gut microbiome and soil environments harbor dense, polymicrobial communities where frequent interbacterial interactions and contact-dependent responses occur between community members. Two phyla abundant in these niches, Gram-negative Bacteroidota and Gram-positive Bacillota, utilize contact-dependent type VI and type VII secretion systems (T6SS and T7SS), respectively, to deliver antagonistic toxins (effectors) during competitive encounters with neighboring bacteria. However, the mechanisms of interbacterial antagonism mediated by T6SS and T7SS, as well as proteomic responses to interbacterial contacts, remain underexplored in these ecosystems. Here, we reveal the widespread distribution of the T6SS- DNAse effector (Tde) and its cognate immunity protein (Tdi) amongst gut commensal Bacteroidota species and soil-derived Bacillota species. Structural and functional analyses demonstrate that Tde1 possesses nuclease activity that elicits T6SS-dependent toxicity among Bacteroidaceae strains. Despite sequence differences, the Tde proteins from Bacillota and Bacteroidota phyla exhibited high structural similarities. The crystal structures of isolated Tde and several Tde/Tdi complexes highlight a conserved inactivation mechanism across these two phyla, whereby Tdi immunity proteins bind the effector and disrupt its nuclease fold, except Enterococcus quebeciensis, which displayed slight differences with Tde C-terminus flexibility upon binding to the cognate immunity protein. The Tde/Tdi interaction mode represents a novel mechanism of inactivation distinct from other polymorphic toxin-immunity pairs of known structure. AAA family ATPases in Bacteroides ovatus are downregulated in response to contact with T6SS encoding Bacteroides strains. Deletion of these AAA ATPases alters the response to Tde delivered by T6SS, suggesting roles for these ATPases in responding to T6SS-mediated attack. Our findings reveal that horizontally transferred Tde-encoding T6SS loci confer a competitive advantage to Bacteroidales. The unique Tde/Tdi interaction suggests that Tdi homologs can provide broad immunity by disrupting the conserved Tde fold.
Details
- Title: Subtitle
- Defense against bacterial toxin secretion systems
- Creators
- Romina Abbasian
- Contributors
- Dustin E Bosch (Advisor)Ashutosh K Mangalam (Committee Member)Botond Banfi (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Pathology
- Date degree season
- Autumn 2023
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.006929
- Number of pages
- x, 82 pages
- Copyright
- Copyright 2023 Romina Abbasian
- Comment
This thesis has been optimized for improved web viewing. If you require the original version, contact the University Archives at the University of Iowa: https://www.lib.uiowa.edu/sc/contact/.
- Language
- English
- Date submitted
- 11/03/2023
- Description illustrations
- illustrations, graphs
- Description bibliographic
- Includes bibliographical reference (pages 74-82).
- Public Abstract (ETD)
- The human gut contains a dense community of bacteria (known as the microbiome) that affects human health. Disruption of the microbiome composition can contribute to diseases such as inflammatory bowel disease. Bacteria in the microbiome frequently interact with one another through cell-cell contacts. Contact-dependent bacterial interactions alter the gut microbiome makeup, which has been linked to various diseases. One example of bacterial interaction involves toxin-delivery systems that help bacteria compete for nutrients and space. Here, we characterize a toxin family abundantly found in two major gut bacterial groups, Bacteroidota and Bacillota, and demonstrate its role in cell killing between different bacteria. We also identify protective strategies that competing bacteria have developed to counteract this toxin's effects. Our work describes a prevalent toxin and corresponding defense systems that may modulate the gut bacterial community. Identifying factors that disrupt the healthy microbiome can provide targets for treating illnesses like inflammatory bowel disease in the future. In sum, our study elucidates bacterial competition and defense dynamics that likely influence human health.
- Academic Unit
- Pathology
- Record Identifier
- 9984546750502771
Metrics
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