The bifunctional dynamin-like GTPase switch DynAB modulates both vegetative and sporulation cell division in Streptomyces.

Abstract

As part of their complex developmental lifecycle, the multicellular filamentous bacteria Streptomyces have evolved two modes of cell division distinct from binary fission. In vegetative cell division, irregularly spaced cross-walls form within vegetative hyphae, whereas in sporogenic hyphae, regularly spaced sporulation septa form synchronously, leading to spore formation. However, the mechanisms controlling these processes largely remain unknown. The bacterial dynamin-like protein pair DynAB was previously reported to be a component of sporulation septa. Here, we reveal that DynA and DynB have critical roles in both cell division modes, regulating the formation of sporulation septa and cross-walls, with the Streptomyces cell division protein SsgB modulating their activities. dynAB deletion and overexpression, respectively, increased and abrogated cross-wall formation in vegetative hyphae, and Streptomyces DynAB also inhibited cell division in Escherichia coli, resulting in formation of unicellular filamentous cells and suggesting an ancient and conserved function for these proteins. Notably, SsgB could relieve the inhibition of cell division by DynAB in both Streptomyces and E. coli. In contrast to DynAB, SsgB overexpression generated spore-like compartments in vegetative hyphae, a phenomenon that required disruption of the DynAB complex. Fluorescent tags revealed dynamic localization of DynAB during development, and further analyses indicated that, in sporogenic hyphae, the timing of DynAB expression, their GTP-binding activity, and interaction with SsgB were associated with the synchronous initiation of sporulation septation. Our findings establish DynAB as an integrator of spatiotemporal cues in bacterial multicellularity and provide insights into the evolution of complex cell cycle regulation in prokaryotes. SignificanceThe evolution of multicellularity in bacteria involved the development of complex mechanisms to spatially and temporally coordinate cell division. Streptomyces, renowned for their production of bioactive secondary metabolites, exemplify bacterial complexity. This study reveals how Streptomyces employ the dynamin-like proteins DynAB as a bifunctional molecular switch, enabling transition between vegetative and reproductive growth through integrated interactions with developmentally regulated proteins and the availability of the energy supplier GTP. Importantly, DynAB could repress cell division in both Streptomyces and Escherichia coli, suggesting an evolutionary origin of these proteins prior to bacterial multicellularity. Our work reveals the dual function and switch mechanism of DynAB in Streptomyces, providing insights into the emergence of dynamic cell cycle control in prokaryotes.