Modular Lipoprotein Toxins Transferred by Outer Membrane Exchange Target Discrete Cell Entry Pathways
Open Access
- 26 October 2021
- journal article
- research article
- Published by American Society for Microbiology in mBio
- Vol. 12 (5), e0238821
- https://doi.org/10.1128/mbio.02388-21
Abstract
Bacteria compete against related individuals by delivering toxins. In myxobacteria, a key delivery and kin discrimination mechanism is called outer membrane (OM) exchange (OME). Here, cells that display compatible polymorphic cell surface receptors recognize one another and bidirectionally transfer OM content. Included in the cargo is a suite of polymorphic SitA lipoprotein toxins. Consequently, OME between compatible cells that are not clonemates results in intoxication, while exchange between clonemates is harmonious because cells express a cognate repertoire of immunity proteins, which themselves are not transferred. SitA toxins belong to six nonhomologous families classified by sequence conservation within their N-terminal "escort domains" (EDs), while their C termini contain polymorphic nucleases that target the cytoplasmic compartment. To investigate how toxins delivered to the OM by OME translocate to the cytoplasm, we selected transposon mutants resistant to each family. Our screens identified eight genes that conferred resistance in a SitA family-specific manner. Most of these genes are predicted to localize to the cell envelope, and some resemble proteins that colicins exploit to gain cell entry. By constructing functional chimeric SitAs between families, we show that the ED determines the specificity of resistance. Importantly, a mutant that confers resistance to all six SitA families was discovered. This gene was named traC and plays an accessory role with traM in OME. This work thus provides insight into the mechanism of kin discrimination in myxobacteria and provides working models for how SitA toxins exploit host proteins to gain cytoplasmic entry. IMPORTANCE Many bacterial species use diverse systems to deliver bacteriocins or toxins to neighboring competing cells. These systems are often selective in targeting cells that are related to themselves and therefore compete in the same niches for resources. How these systems specifically identify target cells and deliver toxins to particular cellular compartments is a fundamental question. This study uses the model social bacterium Myxococcus xanthus to unravel how its kin discrimination system, called outer membrane exchange, works. Along with the TraA polymorphic cell surface receptor that identifies related individuals with compatible receptors, this work discovered a new protein, called TraC, that functions in this discrimination system. Additionally, genetic screens identified host factors that are proposed to be involved in the cytoplasmic entry of lipoprotein toxins from the OM. This work complements and broadens our mechanistic understanding of how bacteria use transport systems to discriminate against related foes to build clonal populations.Funding Information
- HHS | NIH | National Institute of General Medical Sciences (GM101449, GM140886)
This publication has 58 references indexed in Scilit:
- Two Systems for Conditional Gene Expression in Myxococcus xanthus Inducible by Isopropyl-β- d -Thiogalactopyranoside or VanillateJournal of Bacteriology, 2012
- Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomicsBiology Direct, 2012
- Identification of the cglC , cglD , cglE , and cglF Genes and Their Role in Cell Contact-Dependent Gliding Motility in Myxococcus xanthusJournal of Bacteriology, 2012
- Heterologous protein transfer within structured myxobacteria biofilmsMolecular Microbiology, 2011
- New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0Systematic Biology, 2010
- The colicin Ia receptor, Cir, is also the translocator for colicin IaMolecular Microbiology, 2009
- DNA phosphorothioation in Streptomyces lividans: mutational analysis of the dnd locusBMC Microbiology, 2009
- Jalview Version 2—a multiple sequence alignment editor and analysis workbenchBioinformatics, 2009
- MutL homologs in restriction-modification systems and the origin of eukaryotic MORC ATPasesBiology Direct, 2008
- Cell-to-Cell Transfer of Bacterial Outer Membrane LipoproteinsScience, 2005