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Abstract:
Myxococcus xanthus serves as a prokaryotic model organism for the regulation of complex social behaviors. During all aspects of its life cycle M. xanthus favors multicellular behavior, including a developmental program in which the population is segregated into at least three distinct cell fates (sporulation inside multicellular fruiting bodies, peripheral rods and cell lysis). Neither the evolutionary advantage of producing these distinct cell fates, nor the mechanism by which cell fate segregating is induced are fully understood. However, MrpC, a major developmental trans-criptional regulator, is a good candidate for the regulation of cell fate segregation. MrpC accumulation is controlled by multiple distinct signaling systems including the (orphan) histidine protein kinases (HPKs) Esp, TodK, Red and Hpk30. A strain lacking three of the pathways (Δesp Δred ΔtodK) massively over-accumulates MrpC and displays a striking phenotype in which all cells appear to sporulate inappropriately rapidly, producing lawns of spores. In this thesis research, I first report how M. xanthus benefits from production of spores inside of fruiting bodies. I next address how fruiting body formation and cell fate segregation can be controlled. To do so, I characterized the mechanisms by which Red, TodK and Hpk30 could control MrpC accumulation. We have previously observed that a strain lacking Esp, Red and TodK signaling systems is deficient in the formation of organized fruiting bodies and essentially produces lawns of spores. By taking advantage of this mutant strain, I addressed the role of cell fate segregation in dispersal and environmental resistance of M. xanthus fruiting bodies. I showed that loss of fruiting body morphology leads to enhanced dispersal by the vector Drosophila melanogaster. However, this comes at the expense of environmental resistance as could be demonstrated by the impact of UV exposure on mutant and wild type fruiting bodies as well as wild type single spores. To clarify how signaling systems may converge to regulate MrpC accumulation, I confirmed a putative connection between the Red signaling system and the Ser/Thr kinase cascade thought to control MrpC activity by phosphorylation. To start to identify possible mechanisms by which TodK and Hpk30 could affect MrpC accumulation, I carried out a detailed characterization of their respective signal flows. TodK functions as a bifunctional histidine protein kinase/phosphatase, whose activity is likely modulated by the two N-terminal PAS-domains. Hpk30 characterization revealed kinase activity as the signal output and that this activity is modulated by its two receiver domains as well as a hypothetical protein, MXAN_4466. Together, these data suggest a model in which separate signaling systems converge to regulate MrpC accumulation in distinct cell types leading to segregation of cells into either peripheral rods outside or spores inside fruiting bodies. Altering the spatial and/or temporal accumulation of MrpC within cells in the developing population is used to adapt fruiting body morphology to specific environmental conditions in which either dispersal or long-term resistance might enhance M. xanthus survival.
