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Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins
Sean Carim1, Ashley L Azadeh2, Alexey E Kazakov3
1Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.
Abstract:
Tailocins are bactericidal protein complexes produced by a wide variety of bacteria that kill closely related strains and may play a role in microbial community structure. Thanks to their high specificity, tailocins have been proposed as precision antibacterial agents for therapeutic applications. Compared to tailed phages, with whom they share an evolutionary and morphological relationship, bacterially produced tailocins kill their host upon production but producing strains display resistance to self-intoxication. Though lipopolysaccharide (LPS) has been shown to act as a receptor for tailocins, the breadth of factors involved in tailocin sensitivity, and the mechanisms behind resistance to self-intoxication, remain unclear. Here, we employed genome-wide screens in four non-model pseudomonads to identify mutants with altered fitness in the presence of tailocins produced by closely related pseudomonads. Our mutant screens identified O-antigen composition and display as most important in defining sensitivity to our tailocins. In addition, the screens suggest LPS thinning as a mechanism by which resistant strains can become more sensitive to tailocins. We validate many of these novel findings, and extend these observations of tailocin sensitivity to 130 genome-sequenced pseudomonads. This work offers insights into tailocin-bacteria interactions, informing the potential use of tailocins in microbiome manipulation and antibacterial therapy.
Insights
Tailocins, bacterial toxins, target specific strains. Their O-antigen and lipopolysaccharide (LPS) structure are key to sensitivity, offering potential for precision antibacterial therapies and microbiome control.
Area of Science:
- Microbiology
- Bacteriology
- Genomics
Background:
- Tailocins are protein complexes from bacteria that kill related strains, influencing microbial communities.
- Their high specificity suggests potential as precision antibacterial agents.
- Lipopolysaccharide (LPS) is a known tailocin receptor, but sensitivity factors and resistance mechanisms are not fully understood.
Purpose of the Study:
- To identify genetic factors influencing bacterial sensitivity to tailocins.
- To elucidate mechanisms of tailocin resistance in producing strains.
- To explore tailocin applications in microbiome manipulation and therapy.
Main Methods:
- Genome-wide screens were performed in four non-model pseudomonad species to find mutants with altered tailocin sensitivity.
- Mutant fitness was assessed in the presence of tailocins from closely related pseudomonads.
- Findings were validated and extended to 130 sequenced pseudomonad genomes.
Main Results:
- O-antigen composition and display were identified as critical determinants of tailocin sensitivity.
- LPS thinning was suggested as a mechanism for increased tailocin sensitivity in resistant strains.
- Novel insights into tailocin-bacteria interactions and sensitivity determinants were uncovered.
Conclusions:
- Tailocin sensitivity is significantly influenced by O-antigen and LPS structure.
- Understanding these interactions can guide the development of tailocin-based antibacterial strategies.
- This research provides a foundation for utilizing tailocins in therapeutic and microbiome applications.
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