scholarly journals Streptomyces: A Screening Tool for Bacterial Cell Division Inhibitors

2014 ◽  
Vol 20 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Charul Jani ◽  
Elitza I. Tocheva ◽  
Scott McAuley ◽  
Arryn Craney ◽  
Grant J. Jensen ◽  
...  
Keyword(s):  
Cell Division ◽  
Stress Responses ◽  
Screening Tool ◽  
Streptomyces Coelicolor ◽  
Sos Response ◽  
Spore Formation ◽  
Bacterial Cell Division ◽  
Distinct Cell ◽  
Chemical Inhibitors ◽  
Complete Cell

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.

scholarly journals Dynamic interplay of ParA with the polarity protein, Scy, coordinates the growth with chromosome segregation in Streptomyces coelicolor

Open Biology ◽  
2013 ◽  
Vol 3 (3) ◽  
pp. 130006 ◽  
Author(s):  
Bartosz Ditkowski ◽  
Neil Holmes ◽  
Joanna Rydzak ◽  
Magdalena Donczew ◽  
Martyna Bezulska ◽  
...  
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Tip Growth ◽  
Streptomyces Coelicolor ◽  
Proximal Region ◽  
Cytoskeletal Protein ◽  
Mutant Form ◽  
Bacterial Cell Division ◽  
Aerial Hyphae ◽  
Dynamic Interplay

Prior to bacterial cell division, the ATP-dependent polymerization of the cytoskeletal protein, ParA, positions the newly replicated origin-proximal region of the chromosome by interacting with ParB complexes assembled on parS sites located close to the origin. During the formation of unigenomic spores from multi-genomic aerial hyphae compartments of Streptomyces coelicolor , ParA is developmentally triggered to form filaments along the hyphae; this promotes the accurate and synchronized segregation of tens of chromosomes into prespore compartments. Here, we show that in addition to being a segregation protein, ParA also interacts with the polarity protein, Scy, which is a component of the tip-organizing centre that controls tip growth. Scy recruits ParA to the hyphal tips and regulates ParA polymerization. These results are supported by the phenotype of a strain with a mutant form of ParA that uncouples ParA polymerization from Scy. We suggest that the ParA–Scy interaction coordinates the transition from hyphal elongation to sporulation.

scholarly journals Streptomyces coelicolor Genes ftsL and divIC Play a Role in Cell Division but Are Dispensable for Colony Formation

2007 ◽  
Vol 189 (24) ◽  
pp. 8982-8992 ◽  
Author(s):  
Jennifer A. Bennett ◽  
Rachel M. Aimino ◽  
Joseph R. McCormick
Keyword(s):  
Cell Division ◽  
Double Mutant ◽  
Minimal Medium ◽  
Streptomyces Coelicolor ◽  
Bacterial Cell Division ◽  
Transmission Electron ◽  
Aerial Hyphae ◽  
Mutant Strains ◽  
High Sucrose ◽  
Insertion Mutations

ABSTRACT We have characterized homologues of the bacterial cell division genes ftsL and divIC in the gram-positive mycelial bacterium Streptomyces coelicolor A3(2). We show by deletion-insertion mutations that ftsL and divIC are dispensable for growth and viability in S. coelicolor. When mutant strains were grown on a conventional rich medium (R2YE, containing high sucrose), inactivation of either ftsL or divIC resulted in the formation of aerial hyphae with partially constricted division sites but no clear separation of prespore compartments. Surprisingly, this phenotype was largely suppressed when strains were grown on minimal medium or sucrose-free R2YE, where division sites in many aerial hyphae had finished constricting and chains of spores were evident. Thus, osmolarity appears to affect the severity of the division defect. Furthermore, double mutant strains deleted for both ftsL and divIC are viable and have medium-dependent phenotypes similar to that of the single mutant strains, suggesting that functions performed by FtsL and DivIC are not absolutely required for septation during growth and sporulation. Alternatively, another division protein may partially compensate for the loss of both FtsL and DivIC on minimal medium or sucrose-free R2YE. Finally, based on transmission electron microscopy observations, we propose that FtsL and DivIC are involved in coordinating symmetrical annular ingrowth of the invaginating septum.

scholarly journals SepG coordinates sporulation-specific cell division and nucleoid organization in Streptomyces coelicolor

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150164 ◽  
Author(s):  
Le Zhang ◽  
Joost Willemse ◽  
Dennis Claessen ◽  
Gilles P. van Wezel
Keyword(s):  
Cell Division ◽  
Transmembrane Protein ◽  
Streptomyces Coelicolor ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Direct Interaction ◽  
Specific Cell ◽  
Bacterial Cell Division ◽  
Reporter System ◽  
Complex Process

Bacterial cell division is a highly complex process that requires tight coordination between septum formation and chromosome replication and segregation. In bacteria that divide by binary fission a single septum is formed at mid-cell, a process that is coordinated by the conserved cell division scaffold protein FtsZ. In contrast, during sporulation-specific cell division in streptomycetes, up to a hundred rings of FtsZ (Z rings) are produced almost simultaneously, dividing the multinucleoid aerial hyphae into long chains of unigenomic spores. This involves the active recruitment of FtsZ by the SsgB protein, and at the same time requires sophisticated systems to regulate chromosome dynamics. Here, we show that SepG is required for the onset of sporulation and acts by ensuring that SsgB is localized to future septum sites. Förster resonance energy transfer imaging suggests direct interaction between SepG and SsgB. The beta-lactamase reporter system showed that SepG is a transmembrane protein with its central domain oriented towards the cytoplasm. Without SepG, SsgB fails to localize properly, consistent with a crucial role for SepG in the membrane localization of the SsgB–FtsZ complex. While SsgB remains associated with FtsZ, SepG re-localizes to the (pre)spore periphery. Expanded doughnut-shaped nucleoids are formed in sepG null mutants, suggesting that SepG is required for nucleoid compaction. Taken together, our work shows that SepG, encoded by one of the last genes in the conserved dcw cluster of cell division and cell-wall-related genes in Gram-positive bacteria whose function was still largely unresolved , coordinates septum synthesis and chromosome organization in Streptomyces .

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

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