title: Streptomyces: a screening tool for bacterial cell division inhibitors.
abstract: Cell division is essential for spore formation but not for viability in the filamentous streptomycetes bacteria. Failure to complete cell division instead blocks spore formation, a phenotype that can be visualized by the absence of gray (in Streptomyces coelicolor) and green (in Streptomyces venezuelae) spore-associated pigmentation. Despite the lack of essentiality, the streptomycetes divisome is similar to that of other prokaryotes. Therefore, the chemical inhibitors of sporulation in model streptomycetes may interfere with the cell division in rod-shaped bacteria as well. To test this, we investigated 196 compounds that inhibit sporulation in S. coelicolor. We show that 19 of these compounds cause filamentous growth in Bacillus subtilis, consistent with impaired cell division. One of the compounds is a DNA-damaging agent and inhibits cell division by activating the SOS response. The remaining 18 act independently of known stress responses and may therefore act on the divisome or on divisome positioning and stability. Three of the compounds (Fil-1, Fil-2, and Fil-3) confer distinct cell division defects on B. subtilis. They also block B. subtilis sporulation, which is mechanistically unrelated to the sporulation pathway of streptomycetes but is also dependent on the divisome. We discuss ways in which these differing phenotypes can be used in screens for cell division inhibitors.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Michael DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
authors.forename: Charul
authors.initials: C
authors.lastname: Jani
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
authors.forename: Elitza I
authors.initials: EI
authors.lastname: Tocheva
authors.affiliation: Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: McAuley
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Michael DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
authors.forename: Arryn
authors.initials: A
authors.lastname: Craney
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA Howard Hughes Medical Institute, Chevy Chase, MD, USA.
authors.forename: Grant J
authors.initials: GJ
authors.lastname: Jensen
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Michael DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada Department of Biochemistry, University of Toronto, Toronto, ON, Canada justin.nodwell@utoronto.ca.
authors.forename: Justin
authors.initials: J
authors.lastname: Nodwell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods*; D013014:SOS Response, Genetics / Q000187:drug effects; D054852:Small Molecule Libraries; D013302:Streptomyces / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries
keywords: Streptomyces; bacterial cell division; cell-based assays; in vivo screening; sporulation