Abstract
Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. Sporulation in the absence of fruiting bodies can be artificially induced by high concentrations of glycerol through unclear mechanisms. Here, we show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M. xanthus in a similar manner. Both glycerol (at millimolar levels) and ambruticin VS-3 (at nanomolar concentrations) inhibit M. xanthus fruiting body formation under starvation, and induce sporulation in the presence of nutrients. The response is mediated in M. xanthus by three hybrid histidine kinases (AskA, AskB, AskC) that form complexes interacting with two major developmental regulators (MrpC, FruA). In addition, AskB binds directly to the mrpC promoter in vitro. Thus, our work indicates that the AskABC-dependent regulatory pathway mediates the responses to ambruticin VS-3 and glycerol. We hypothesize that production of ambruticin VS-3 may allow S. sorangium to outcompete M. xanthus under both starvation and growth conditions in soil.
Highlights
Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores
Motivated by observing a striking inability of M. xanthus to form fruiting bodies (FB) when co-cultivated with Sorangium cellulosum, we initiated research to identify the factor causing this interspecies interaction and here provide evidence that the antifungal ambruticin VS-3 is a “natural” chemical inducer of sporulation
We show that ambruticin VS-3 acts as inhibitor of FB formation and starvation-induced sporulation at low nanomolar concentrations
Summary
Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. We show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M. xanthus in a similar manner Both glycerol (at millimolar levels) and ambruticin VS-3 (at nanomolar concentrations) inhibit M. xanthus fruiting body formation under starvation, and induce sporulation in the presence of nutrients. We hypothesize that production of ambruticin VS-3 may allow S. sorangium to outcompete M. xanthus under both starvation and growth conditions in soil Besides their large potential to produce bioactive compounds, myxobacteria are excellent model organisms to study cell-tocell signaling and gene regulation during a complex life cycle involving multicellular development. This could be shown by both, the altered binding of MrpC in the presence of ambruticin VS-3 and kinase AskB that binds preferentially to DNA comprising promoter PmrpC in vitro
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