Cause and consequences of multicellularity in Streptomyces

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Streptomyces are our most prolific antibiotic producers and represent an excellent, genetically tractable system to study bacterial multicellularity. During their vegetative growth, they exist as a network of interconnected multicellular filaments containing cross-walls that separate the hypha into compartments but do not lead to cell fission. The filamentous form gives rise to the formation of multi-hyphal mycelial pellets that further develop into structured colonies in which division of labour determines which subpopulation initiates sporulation for reproduction and which fraction of cells produces antibiotics for nutrient protection released by coordinated apoptosis. However, the molecular mechanisms and the evolutionary benefits driving the multi-dimensional multicellularity in the genus Streptomyces are not well understood.In this interdisciplinary proposal, the synergetic combination of a molecular microbiologist and an evolutionary biologist provides a unique possibility to study the molecular factors that determine Streptomyces multicellularity and analyse the fitness benefits of transitions between unicellular and multicellular morphologies. The molecular perspective of the proposed research builds on preliminary suppressor analysis identifying the nucleoid-associated protein Lsr2 and the transcriptional regulator SsgR as key factors that determine the switch from uni- to multicellular existence. The spectrum of relevant molecular control elements of multicellularity will be extended by using phenotypic manipulation in experimental evolution. The effects of form and architecture on fitness of strains with ranging morphologies from uni- to multicellularity will be analysed in resource conversion studies and head-to-head competitions. We will quantify how altered size and morphology affects antibiotic synthesis and labour division and study how hyphal death affects intracellular transport. Altogether, our combined expertise and strong preliminary data represent a uniquely powerful baseline to improve our understanding of genetics and evolutionary consequences of bacterial multicellularity. We may also reveal new approaches to manipulate multicellular phenotypes in order to increase the productivity and diversity of industrially important products made by streptomycetes, like antibiotics and enzymes, for human benefit.