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. The
streptomycetes divisome is however, similar to that of other prokaryotes.
We hypothesized chemical inhibitors of sporulation in model streptomycetes might
interfere with cell division in rod shaped bacteria. To test this, we investigated 196
compounds that inhibit sporulation in Streptomyces 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, 2 and 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 which is also dependent on the divisome. We
discuss ways in which these differing phenotypes can be used in screens for cell division
inhibitors.
In addition to the molecules affecting the divisome, DNA and cell wall damage also
affects the process indirectly by temporarily halting the cell division. To further explore
the cell division regulation in stressful conditions, we carried the complete transcriptomic analysis of S. venezuelae after the DNA damage. The observed changes in the gene
expression as a result of the DNA damage paves the way for identification of the DNAdamage
induced cell division inhibitor in streptomycetes. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18466 |
| Date | January 2015 |
| Creators | Jani, Charul |
| Contributors | Nodwell, Justin, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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