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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
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Modular Lipoprotein Toxins Transferred by Outer Membrane Exchange Target Discrete Cell Entry Pathways
Christopher N Vassallo1, Govind Prasad Sah1, Michael L Weltzer1
1Department of Molecular Biology, University of Wyominggrid.135963.b, Laramie, Wyoming, USA.
Mbio
|September 14, 2021
Summary
Bacteria use outer membrane exchange (OME) to deliver toxins, but distinguish kin from foes. This study identified new proteins, including TraC, involved in this kin discrimination and toxin entry mechanism in Myxococcus xanthus.
Area of Science:
- Bacterial competition and social behavior
- Cell-cell communication and toxin delivery
- Molecular mechanisms of bacterial warfare
Background:
- Bacteria compete using toxins, with Myxobacteria employing outer membrane exchange (OME) for kin discrimination.
- OME involves bidirectional transfer of outer membrane content, including SitA lipoprotein toxins, between compatible cells.
- OME distinguishes clonemates (harmonious exchange) from non-clonemates (intoxication) via polymorphic cell surface receptors and immunity proteins.
Purpose of the Study:
- To investigate the mechanism by which SitA toxins, delivered via OME, translocate from the outer membrane to the cytoplasm.
- To identify host factors involved in SitA toxin entry into the cytoplasm.
- To elucidate the molecular basis of kin discrimination in Myxococcus xanthus.
Main Methods:
- Selection of transposon mutants resistant to different SitA toxin families.
- Construction of functional chimeric SitA toxins between families.
- Genetic screens to identify genes conferring resistance to SitA toxins.
- Analysis of the role of newly identified genes, including traC, in OME and toxin resistance.
Main Results:
- Eight genes conferring SitA family-specific resistance were identified, many localizing to the cell envelope.
- The N-terminal escort domain (ED) of SitA toxins was shown to determine resistance specificity.
- A novel gene, traC, was discovered to confer resistance to all six SitA families and plays an accessory role in OME.
- traC, along with traAB, is implicated in the Myxococcus xanthus kin discrimination system.
Conclusions:
- SitA toxins likely exploit host cell envelope proteins for cytoplasmic entry.
- The escort domain of SitA toxins dictates resistance specificity.
- TraC is a novel component of the OME system, crucial for kin discrimination and potentially toxin translocation.
- This research provides insights into bacterial warfare strategies and the mechanisms of toxin delivery and cellular entry.
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