Department of Molecular Biology
University of Wyoming
Laramie, WY 82071
A fundamental question in biology is how do individual cells within a multicellular organism interact to coordinate diverse processes? We are interested in this question from molecular and evolutionary perspectives. To address this topic our laboratory studies the genetically tractable organism called Myxococcus xanthus. As a group, myxobacteria are highly social microbes that move, hunt and develop as coherent multicellular units. Their most notable behavior is their ability to build fruiting bodies in response to starvation. Here, thousands of individual and small groups of cells coalesce from their environment to assemble fruiting bodies wherein vegetative cells differentiate into environmentally resistant spores (Fig. 1). In this regard our laboratory is focused on two questions: (i) How does molecular or kin recognition occur between cells? (ii) How, in mechanistic and evolutionary terms, can myxobacteria transition between solitary and multicellular lifestyles?
Fig. 1. Fruiting body development. A) Model of fruiting body formation by M. xanthus cells (yellow) from a diverse microbial community. B) Micrograph of an actual Chondromyces crocatus fruiting body.
We propose that a partial answer to the above questions lies within a novel process that we discovered and named – outer membrane exchange (OME). Here, upon physical contact with a neighboring cell the outer membranes will transiently fuse and the cells will exchange outer membrane proteins and lipids (Fig. 2). OME is mediated by the TraA cell surface receptor and the TraB cohort protein, which are involved in cell-cell adhesion and membrane fusion. The exchange or sharing of significant amounts of cellular resources within diverse microbial communities (soil) raises questions about how partner cells are identified and whether these interactions are regulated. Indeed, we have found that OME is highly selective and only occurs between cells that contain identical or nearly identical TraA proteins. Therefore OME is a form of kin recognition that is governed by genetically defined homotypic interactions between polymorphic traA alleles. Thus cells that express identical or nearly identical traA alleles form a functional recognition group, while strains with divergent TraA receptors will not exchange (Fig. 3). Molecular and phylogenetic studies further suggest that among environmental populations there is hundreds of different TraA-derived recognition or social groups. Phenotypically, Tra-dependent OME leads to both beneficial and adversarial outcomes. For instance, under certain conditions damaged proteins or lipopolysaccharides in the cell envelop can be repaired by healthy partner cells, which represents a cooperative behavior. In contrast, under other conditions OME can lead to ‘policing’ or lethal consequences. These latter outcomes have likely driven the formation polymorphisms found in TraA and different kin groups. In summary, we view OME as a new paradigm for how bacterial cells can communicate, interact and transition from individuals into functional multicellular units. Our future studies are aimed at understanding the molecular details of cell-cell recognition, mechanism of outer membrane fusion and the social and evolutionary consequences of OME.
Fig. 2. Model for outer membrane exchange (OME) in myxobacteria. A) TraA mediated interactions between two cell poles is illustrated. Homotypic interactions between two compatible TraA proteins lead to the exchange of outer membrane proteins and lipids. B) Detailed model of outer membrane fusion between two cells during OME.
Fig. 3. Schematic overview for how OME might contribute toward myxobacterial social behaviors. Colored arrowheads represent different TraA receptors involved in cell-cell recognition. TraA receptors recognize kin cells that lead to OME and social consequences.
Postdoctoral Fellow, Stanford University, 1998
Ph.D., University of Utah, 1994
B.A., Sonoma State University, 1988
Associate Professor, University of Wyoming, Current
Principal Scientist, Anadys Pharmaceuticals, 2006
Senior Scientist, Elitra Pharmaceuticals, 2002
Wall, D. 2016. Kin recognition in bacteria. Annu. Rev. Microbiol. http://www.annualreviews.org/doi/abs/10.1146/annurev-micro-102215-095325?src=recsys
Vassallo, C. and Wall, D. 2016. Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage. BioEssays 38:306-315.
Dey, A., Vassallo, C. N., Conklin, A. C., Pathak, D. T., Troselj, and Wall, D. 2016. Sibling rivalry in Myxococcus xanthus is mediated by kin recognition and a polyploid prophage. J. Bacteriol. 198:994-1004.
Cao, P., Dey, A., Vassallo C. and Wall, D. 2015. How myxobacteria cooperate. J. Mol. Biol. 427:3709-3721.
Vassallo C., Pathak D.T., Cao P., Zuckerman, D.M., Hoiczyk, E. and Wall, D. 2015. Cell rejuvenation and social behaviors promoted by LPS exchange in myxobacteria. PNAS. 112(22):E2939-46.
Dey, A. and Wall, D. 2014. A genetic screen in Myxococcus xanthus identifies mutants that uncouple outer membrane exchange from a downstream cellular response. J. Bacteriol. 196:4324-4332.
Wall, D. 2014. Molecular recognition in myxobacterial outer membrane exchange: Functional, social and evolutionary implications. Mol. Microbiol. 91:209-220.
Xiao, Y. and Wall, D. 2014. Genetic redundancy and proximity of lspA, the target of antibiotic TA, in the Myxococcus xanthus producer strain genome. J. Bacteriol. 196:1174-1183.
Wei, X., Vassallo, C.N., Pathak, D.T. and Wall, D. 2014. Myxobacteria produce outer membrane enclosed tubes in unstructured environments. J. Bacteriol. 196:1807-1814.
Wall, D. 2014. Social interactions mediated by outer membrane exchange. In Myxobacteria: Genomics, Cellular and Molecular Biology, edited by Yang, Z. & Higgs, P.I., Caister Academic Press, Norwich, U.K., pp 91-103.
Wall, D. 2014. DNA Cloning Strategies. In Reference Module in Biomedical Sciences, Elsevier Ltd, Oxford, U.K., doi:10.1016/B978-0-12-801238-3.02500-9.
Pathak, D.T., Wei, X., Dey, A. and Wall, D. 2013. Molecular recognition by a polymorphic cell surface receptor governs cooperative behaviors in bacteria. PLoS Genet. 9:e1003891.
Pathak, D.T., Wei, X., Bucuvalas, A., Haft, D., Gerloff, D. L. and Wall, D. 2012. Cell contact-dependent outer membrane exchange in myxobacteria: Genetic determinants and mechanism. PLoS Genetics 8:e1002626.
Xiao, Y., Gerth, K., Müller and Wall, D., 2012. Myxobacterium-produced antibiotic TA (myxovirescin) inhibits type II signal peptidase. Antimicrob. Agents Chemother.56:2014-2021.
Pathak, D.T. and Wall, D. 2012. Identification of the cglC, cglD, cglE and cglF genes and their role in cell contact-dependent gliding motility in Myxococcus xanthus. J. Bacteriol. 194:1940-1949.
Pathak, D.T., Wei, X. and Wall, D. 2012. Myxobacterial tools for social interactions. Res. Micro. 163:579-591.
Wei, X., Pathak, D. T. and Wall, D., 2011. Heterologous protein transfer within structured myxobacteria biofilms. Mol. Microbiol. 81:315-326.
Xu, H., Trawick, J.D., Haselbeck, R.J., Forsyth, R.A., Yamamoto, R.T., Archer, R., Patterson, J., Allen, M., Froelich, J.M., Taylor, I., Nakaji, D., Maile, R., Kedar, G.C., Pilcher, M., Brown-Driver, V., McCarthy, M., Files, A., Robbins, D., King, P., Sillaots, S., Malone, C., Zamudio, C.S., Roemer, T., Wang, L., Youngman, P.J. and Wall, D. 2010. Staphylococcus aureus TargetArray: Comprehensive differential essential gene expression as a mechanistic tool to profile antibacterials. Antimicrob. Agents Chemother. 54:3659-3670.