Microbial etiquette: Shake hands before trading goods

Go to the profile of Pengbo Cao
Jul 12, 2019
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Single-celled organisms such as bacteria often display complex multicellular traits. For instance, bacteria talk to each other using their own languages. By means of diffusible chemicals or physical contacts, individuals coordinate their behaviors and build social networks. Elucidating how bacteria interact provides a basis to understand how they function as communities and how multicellularity may have evolved. However, it remains a challenge to directly observe the molecular details of bacterial cell-cell interactions and how they assemble into social entities.

In the Wall lab, we address this topic using the model bacterium Myxococcus xanthus, which is known for its complex social behaviors including its ability to form multicellular fruiting bodies in response to starvation. Around the time I joined as a PhD student, the lab uncovered yet another intriguing behavior exhibited by myxobacteria. That is, individual cells exchange their outer membrane (OM) components, including lipids and proteins, when cells make physical contacts and recognize each other as kin. We named this process outer membrane exchange (OME). Two OM proteins, TraA and TraB, were discovered and shown to function as cell surface adhesins that drives cargo transfer. OME among individuals subsequently regulates their cooperative and competitive interactions. However, one important question remained: How do myxobacteria use TraA/B to achieve OME? That is, can we visualize this process in live cells?      

To directly observe OME, I fluorescently tagged the TraA and TraB proteins. In conjunction with structure-function analysis of TraA, I was able to place GFP or mCherry within a dispensable region of TraA while retaining its function. This represented a key milestone since tagging a cell surface receptor like TraA, which is post-translationally processed at the N- and C-termini and transported across two membranes, is a challenging endeavor. What we discovered next was very exciting; when isolated cells bearing TraA, which was uniformly distributed on their surface, made physical contact with another cell, their receptors coalesce at cell-cell junctions! At higher densities, we found that cells within swarms were interconnected through these adhesin clusters, which resemble gap junctions found in eukaryotic tissues. Notably, we also found that these OM adhesins were fluid, which contrasts the prevailing view that OM proteins are relatively immobile and therefore highlights the diverse properties of OMs in gram-negative bacteria.   

Next, we directly observed how myxobacteria use these adhesins in recognition. TraA is highly polymorphic and through homotypic interactions this receptor recognizes related individuals bearing identical or very similar alleles. Interestingly, we observed that compatible TraA receptors from neighboring cells coalesce and colocalize at their junctions. Thus, just like humans, myxobacteria greet their siblings with handshakes when they meet each other! No handshake occurs between two individuals bearing different TraAs. Interestingly, we engineered a myxobacteria strain with two different TraA receptors, and found each receptor acted as a selective “hand” to recognize cognate and distinct social partners. Strikingly, when we fluorescently labeled OM cargo, we found it was transferred immediately after TraA handshakes occurred.

A cartoon illustration of how myxobacteria use a polymorphic receptor to recognize kin and exchange goods.

Our results suggest that OME helps to promote a multicellular lifestyle of myxobacteria. First, TraA/B adhesins, along with other cell surface adhesins and polysaccharides, bind individuals together to form a dynamic and cohesive cell network that resembles eukaryotic tissue. Next, when cells exchange goods, polymorphic toxins are also transferred. These toxins discriminate against non-self that does not harbor the repertoire of cognate immunity proteins. Thus, multicellular cooperation is protected from exploitation by non-kin. Additionally, OME was hypothesized to help maintain population homeostasis. In our study, we tested this idea by mixing two populations whose OMs were differentially labeled.  Strikingly, when these two populations were mixed they merged into one indistinguishable population through OME. In future studies, we will explore whether myxobacteria use OME to exchange information that reflects their prior adaptation experiences to different microenvironments. Such information is presumably encoded in their OM proteome and lipidome. It would also be interesting to see whether myxobacteria can “learn” from each other’s adaptation experiences and modulate their behaviors accordingly to live a more fit and social life. 


Article link: http://disq.us/t/3gi5yyt 

Go to the profile of Pengbo Cao

Pengbo Cao

Postdoc Fellow, Georgia Institute of Technology

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