Myxobacteria Has the Ability to Discriminate Between Self and Non-Self

A basic question in biology is how individual cells hosted by a multicellular organism can engage with each other to arrange various processes.   

A University of Wyoming scientist and his Ph.D. students studied myxobacteria, which are common soil microbes that consume other microbes, and came with the following question: “How do cells from a diverse environment recognize other cells as related or clonal to build social groups and a multicellular organism?”  

“Myxobacteria assemble a multicellular organism by cobbling together cells from their environment. This is in contrast to plants and animals, where gametes fuse to create a unique cell, which, upon clonal expansion, creates a multicellular organism,” says Dan Wall, a professor in the UW Department of Molecular Biology. “The ability of myxobacteria to create multicellular organisms is remarkable, given that soil is considered to be the most diverse environment on the planet, wherein a small sample can consist of tens of thousands of microbial species. Broadly speaking, our work helps to address this question.”  

Wall is co-author of the paper titled ‘Rapid Diversification of Wild Social Groups Driven by Toxin-Immunity Loci on Mobile Genetic Elements,’ which has been published in the International Society for Microbial Ecology (ISME) Journal on June 22nd.   

How Cells Discriminate  

Christopher Vassallo and Vera Troselj, both Ph.D. candidates in Wall’s laboratory back when the research was conducted, are also co-authors of the paper, along with Michael Weltzer, a UW graduate student in the Molecular and Cellular Life Sciences program from Idaho Springs, Colorado.  

This study mostly focuses on fundamental questions and addresses how cells differentiate between the self and non-self, according to Wall.  

“Multicellularity is a difficult way of life to evolve and maintain because cells are the smallest unit of life, and there is selective pressure for them to exploit their environment, including other cells, for their own benefit,” he explains. “For example, cancer cells do this and are constantly arising in our own body. Fortunately, our immune system recognizes them as non-self and eliminates them. Our system works in an analogous manner.”  

According to Wall, his team’s work adds to previous research on the subject that demonstrated a small patch of soil has another layer of incredible diversity at subspecies level. Besides Myxococcus xanthus isolates, the researchers found many different social groups that discriminate against one another. Still, the prior studies did not discover how it works at the molecular level, Wall said.

Different Stages of the Myxobacteria life cycle. [Image: Ronald O. Garcia]
“Our paper addresses the mechanism of how they (myxobacteria) discriminate and how highly related strains recently diverged, or evolved, into distinct social groups,” Wall says.  

The ISME paper also adds to Vassallo and Wall’s previous research, titled ‘Self-Identify Barcodes Encoded in Expansive Polymorphic Toxin Families Discriminate Kin in Myxobacteria,’ that was published in the Proceedings of the National Academy of Sciences (PNAS) on November 19th, 2019.  

New Systems Were Discovered  

The work in the PNAS paper proved that Myxococcus xanthus has a highly variable cell surface receptor dubbed TraA. Cells employ these receptors, which have numerous different sequences or alleles in populations, to identify other cells as possible clonemates or as self.  

If the other cells have identical TRaA receptors, they engage, resulting in the transient fusion of cells where they switch cellular components, including proteins and lipids, as well as highly variable toxin proteins, but no DNA.   

Therefore, if the other cells are indeed clonemates, they have genetically encoded immunity to those toxins. However, if they are dissimilar cells that happen to bear compatible TraA receptors but are not clonemates, they will be killed by the toxin cargo.   

“We analyzed the publicly available genomes of those 22 (myxobacteria) strains, identified their toxin genes, and predicted how they would socially interact,” Wall explained. “We found a perfect correlation between our predictions and empirical findings by others. We then experimentally tested our predictions by creating mutants and showed we could engineer social harmony between otherwise antagonistic strains by inactivating toxin transfer.”  

Besides the TraA delivery/discrimination system, Wall says they have also found two other systems, namely, type VI secretion system (T6SS) and rearrangement hotspot (RHS), which were engaged in kin discrimination. In addition, the group demonstrated that the main discriminatory toxin genes existed on mobile genetic elements in the chromosome.  

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