Metabolic disharmony and sibling conflict mediated by T6SS

Bacteria in nature live in taxonomically complex communities where multitude of species and strains inhabit the same niches and compete for limited resources and space. Surviving in these competitive environments requires mechanisms to recognize and associate with kin and to discriminate against non-kin to increase reproductive success among close relatives. Some of the mechanisms bacteria use to address genetic differences are surface receptors, diffusible signals (e.g. quorum sensing) and toxin-immunity systems (e.g. type VI secretion system (T6SS)). Another way individuals vary within bacterial populations is their physiological states. This means that among clonal cells there is cell-to-cell variability in cells' proteome, growth rates, age and cell damage loads caused by stochastic differences in gene expression/metabolism and variations in microenvironmental stimuli. While physiological heterogeneity benefits some bacteria by allowing populations to bet-hedge their survival odds in changing environments by expressing different phenotypes, it can also be harmful in cases where fitness depends on coordinated behaviors and synchronized actions by many cells; a function of particular importance to social bacteria. Myxococcus xanthus is a non-pathogenic soil bacterium known for its complex social and coordinated behaviors such as swarming, predation and formation of spore-filled fruiting bodies. These behaviors depend on M. xanthus ability to synchronize the actions of many cells within a population. Considering the collective nature of M. xanthus, we asked how do physiological differences affect cell-cell interactions in this species. To address this question, we investigated the interactions between two genetically related but physiologically distinct populations. We found that M. xanthus uses T6SS to eliminate less fit cells from their population and identified toxic effector and cognate immunity protein (TsxEI) that mediates this sibling antagonism.