Edited by Christine Jacobs-Wagner, Yale University, West Haven, CT, and approved October 24, 2019 (received for review July 20, 2019)
Social organisms that share resources must identify their kin to avoid exploitation by nonself competitors; however, underlying mechanisms to explain discrimination are lacking. Myxobacteria, which aggregate into tissue-like groups, use a 2-step self-identification mechanism in which cells interact by a highly variable cell surface receptor that catalyzes cellular cargo exchange. This cargo includes polymorphic toxins that poison nonclonal cells, which lack specific immunity genes. Here, we identified 6 unique families of toxins that are strikingly numerous in myxobacterial genomes. Together, arrays of toxins form what we describe as self-identity barcodes that exquisitely distinguish clonal cooperators from nonself. This work highlights how selfish and discriminating genes, which expand in vast combinations in bacterial genomes, help to diversify and insulate social groups.
Myxobacteria are an example of how single-cell individuals can transition into multicellular life by an aggregation strategy. For these and all organisms that consist of social groups of cells, discrimination against, and exclusion of, nonself is critical. In myxobacteria, TraA is a polymorphic cell surface receptor that identifies kin by homotypic binding, and in so doing exchanges outer membrane (OM) proteins and lipids between cells with compatible receptors. However, TraA variability alone is not sufficient to discriminate against all cells, as traA allele diversity is not necessarily high among local strains. To increase discrimination ability, myxobacteria include polymorphic OM lipoprotein toxins called SitA in their delivered cargo, which poison recipient cells that lack the cognate, allele-specific SitI immunity protein. We previously characterized 3 SitAI toxin/immunity pairs that belong to 2 families. Here, we discover 4 additional SitA families. Each family is unique in sequence, but share the characteristic features of SitA: OM-associated toxins delivered by TraA. We demonstrate that, within a SitA family, C-terminal nuclease domains are polymorphic and often modular. Remarkably, sitA loci are strikingly numerous and diverse, with most genomes possessing >30 and up to 83 distinct sitAI loci. Interestingly, all SitA protein families are serially transferred between cells, allowing a SitA inhibitor cell to poison multiple targets, including cells that never made direct contact. The expansive suites of sitAI loci thus serve as identify barcodes to exquisitely discriminate against nonself to ensure populations are genetically homogenous to conduct cooperative behaviors.
↵1Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
Author contributions: C.N.V. and D.W. designed research; C.N.V. performed research; C.N.V. analyzed data; and C.N.V. and D.W. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1912556116/-/DCSupplemental.
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