Chromosome segregation impacts on cell growth and division site selection in Corynebacterium glutamicum.

Spatial and temporal regulation of bacterial cell division is imperative for the production of viable offspring. In many rod-shaped bacteria, regulatory systems such as the Min system and nucleoid occlusion ensure the high fidelity of midcell divisome positioning. However, regulation of division site selection in bacteria lacking recognizable Min and nucleoid occlusion remains less well understood. Here, we describe one such rod-shaped organism, Corynebacterium glutamicum, which does not always place the division septum precisely at midcell. Here we now show at single cell level that cell growth and division site selection are spatially and temporally regulated by chromosome segregation. Mutants defective in chromosome segregation have more variable cell growth and aberrant placement of the division site. In these mutants, division septa constrict over and often guillotine the nucleoid, leading to nonviable, DNA-free cells. Our results suggest that chromosome segregation or some nucleoid associated factor influences growth and division site selection in C. glutamicum. Understanding growth and regulation of C. glutamicum cells will also be of importance to develop strains for industrial production of biomolecules, such as amino acids

Kosten-Nutzen-Effektivität von Clopidogrel bei akutem Koronarsyndrom: Langzeitbehandlung, sekundäre Prophylaxe, Koronarintervention

Zusammenfassung: Kardiovaskuläre Erkrankungen verursachen weltweit immense Kosten im Gesundheitswesen. Neue Therapieoptionen können Ereignisse und teure Folgehospitalisationen vermeiden. Der Arzt möchte seinen Patienten die bestmögliche Therapie zukommen zu lassen. Bei gestiegenem Kostenbewusstsein besonders im niedergelassenen Bereich ist es jedoch notwendig zu untersuchen, welche Patientengruppen von diesen neuen und häufig ebenfalls kostenintensiven Therapien langfristig profitieren. Diese besonders vor dem Hintergrund der ethischen Verantwortung recht zwiespältige Situation macht Kosten-Nutzen-Untersuchungen auch in der Zukunft unverzichtbar. Der vorliegenden Übersicht kann entnommen werden, in welchen Konstellationen die Gabe von Clopidogrel sowohl auf Kosten- als auch auf medizinischer Nutzenseite besonders geeignet ist. In den meisten hier zitierten Arbeiten erwies sich die Gabe als gerechtfertigt und lag im Rahmen anderer kosteneffektiver Therapien bei kardiovaskulären Krankheite

The MinCDJ System in Bacillus subtilis Prevents Minicell Formation by Promoting Divisome Disassembly

BACKGROUND: Cell division in Bacillus subtilis takes place precisely at midcell, through the action of Noc, which prevents division from occurring over the nucleoids, and the Min system, which prevents cell division from taking place at the poles. Originally it was thought that the Min system acts directly on FtsZ, preventing the formation of a Z-ring and, therefore, the formation of a complete cytokinetic ring at the poles. Recently, a new component of the B. subtilis Min system was identified, MinJ, which acts as a bridge between DivIVA and MinCD. METHODOLOGY/PRINCIPAL FINDINGS: We used fluorescence microscopy and molecular genetics to examine the molecular role of MinJ. We found that in the absence of a functional Min system, FtsA, FtsL and PBP-2B remain associated with completed division sites. Evidence is provided that MinCDJ are responsible for the failure of these proteins to localize properly, indicating that MinCDJ can act on membrane integral components of the divisome. CONCLUSIONS/SIGNIFICANCE: Taken together, we postulate that the main function of the Min system is to prevent minicell formation adjacent to recently completed division sites by promoting the disassembly of the cytokinetic ring, thereby ensuring that cell division occurs only once per cell cycle. Thus, the role of the Min system in rod-shaped bacteria seems not to be restricted to an inhibitory function on FtsZ polymerization, but can act on different levels of the divisome

Pharmacotherapy of Acute Coronary Syndromes: Medical Economics with an Emphasis on Clopidogrel

Summary: Acute coronary syndromes account worldwide for a significant burden of hospital- and societal costs. Pharmacotherapy of acute coronary syndromes consists of a combined antithrombotic therapy. Remarkable therapeutic advances have been made with the introduction of glycoprotein IIb/IIIa receptor inhibitors, low molecular weight heparins and thienopyridines, such as clopidogrel. Based on positive clinical data of large randomized trials numerous cost studies have been undertaken to analyse the cost-effectiveness of these new drugs. Most of them are showing an acceptable level of cost-effectiveness for the new treatments. Taking all available cost-studies into account, we conclude that new antithrombotic treatments are cost-effective as long as their use is limited to selected patient population

Imaging DivIVA dynamics using photo-convertible and activatable fluorophores in Bacillus subtilis

Most rod-shape model organisms such as Escherichia coli or Bacillus subtilis utilize two inhibitory systems for correct positioning of the cell division apparatus. While the nucleoid occlusion system acts in vicinity of the nucleoid, the Min system was thought to protect the cell poles from futile division leading to DNA-free miniature cells. The Min system is composed of an inhibitory protein, MinC, which acts at the level of the FtsZ ring formation. MinC is recruited to the membrane by MinD, a member of the MinD/ParA family of Walker-ATPases. Topological positioning of the MinCD complex depends on MinE in E. coli and MinJ/DivIVA in B. subtilis. While MinE drives an oscillation of MinCD in the E. coli cell with a time-dependent minimal concentration at midcell, the B. subtilis system was thought to be stably tethered to the cell poles by MinJ/DivIVA. Recent developments revealed that the Min system in B. subtilis mainly acts at the site of division, where it seems to prevent reinitiation of the division machinery. Thus, MinCD describe a dynamic behavior in B. subtilis. This is somewhat inconsistent with a stable localization of DivIVA at the cell poles. High resolution imaging of ongoing divisions show that DivIVA also enriches at the site of division. Here we analyze whether polar localized DivIVA is partially mobile and can contribute to septal DivIVA and vice versa. For this purpose we use fusions with green to red photoconvertible fluorophores, Dendra2 and photoactivatable PA-GFP. These techniques have proven very powerful to discriminate protein relocalization in vivo. Our results show that B. subtilis DivIVA is indeed dynamic and moves from the poles to the new septum

A gradient-forming MipZ protein mediating the control of cell division in the magnetotactic bacterium Magnetospirillum gryphiswaldense

Cell division needs to be tightly regulated and closely coordinated with other cellular processes to ensure the generation of fully viable offspring. Here, we investigate division site placement by the cell division regulator MipZ in the alphaproteobacterium Magnetospirillum gryphiswaldense, a species that forms linear chains of magnetosomes to navigate within the geomagnetic field. We show that M. gryphiswaldense contains two MipZ homologs, termed MipZ1 and MipZ2. MipZ2 localizes to the division site, but its absence does not cause any obvious phenotype. MipZ1, by contrast, forms a dynamic bipolar gradient, and its deletion or overproduction cause cell filamentation, suggesting an important role in cell division. The monomeric form of MipZ1 interacts with the chromosome partitioning protein ParB, whereas its ATP-dependent dimeric form shows non-specific DNA-binding activity. Notably, both the dimeric and, to a lesser extent, the monomeric form inhibit FtsZ polymerization in vitro. MipZ1 thus represents a canonical gradient-forming MipZ homolog that critically contributes to the spatiotemporal control of FtsZ ring formation. Collectively, our findings add to the view that the regulatory role of MipZ proteins in cell division is conserved among many alphaproteobacteria. However, their number and biochemical properties may have adapted to the specific needs of the host organism

The RCX extension hub: a resource for implementations extending the R adaption of the cytoscape exchange format

Public repositories provide access to biological networks for investigations, and subsequently serve to distribute the network encoded biomedical and even clinically relevant results. However, inclusion of complementary information requires data structures and implementations customized to the integrated data for network representation, usage in supporting application, and extending analysis functionality. Partitioning of this information into individual aspects of a network facilitates compatibility and reusability of the network-based results, but also requires support and accessibility of the extensions and their implementations. The RCX extension hub offers overview and access to extensions of the Cytoscape exchange format implemented in R. The hub supports the realization of self-customized extension through guides, example implementations, and a template for the creation of R extension packages

An Stomatin, Prohibitin, Flotillin, and HflK/C-Domain Protein Required to Link the Phage-Shock Protein to the Membrane in Bacillus subtilis

Membrane surveillance and repair is of utmost importance to maintain cellular integrity and allow cellular life. Several systems detect cell envelope stress caused by antimicrobial compounds and abiotic stresses such as solvents, pH-changes and temperature in bacteria. Proteins containing an Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH)-domain, including bacterial flotillins have been shown to be involved in membrane protection and membrane fluidity regulation. Here, we characterize a bacterial SPFH-domain protein, YdjI that is part of a stress induced complex in Bacillus subtilis. We show that YdjI is required to localize the ESCRT-III homolog PspA to the membrane with the help of two membrane integral proteins, YdjG/H. In contrast to classical flotillins, YdjI resides in fluid membrane regions and does not enrich in detergent resistant membrane fractions. However, similarly to FloA and FloT from B. subtilis, deletion of YdjI decreases membrane fluidity. Our data reveal a hardwired connection between phage shock response and SPFH proteins