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Cell cycle-regulated surface structures in bacteria

English title Cell cycle-regulated surface structures in bacteria
Applicant Viollier Patrick
Number 162716
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Experimental Microbiology
Start/End 01.10.2015 - 30.09.2018
Approved amount 678'000.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Genetics

Keywords (7)

flagellum; pili; glycosylation; protein localisation; polarity; chemical genetics; capsule

Lay Summary (German)

Lead
Unsere Forschung befasst sich mit der Erkundung neuer Kontrollmechanismen und deren Eiweisse in Bakterien. Unser Interesse gilt besonders den Mechanismen, die einer strikten zeitlicher Kontrolle unterliegen, wie zum Beispiel jene welche bestimmte Vorgänge auf bestimmte Zeitpunkte im Zellzyklus beschränken. Um diese Studien auszuführen, bedienen wir uns des besten Modellsystems für Zellzyklusstudien in Bakterien: dem a-Proteobacterium Caulobacter crescentus.
Lay summary

Studien verschiedener Forschungsgruppen haben erwiesen, dass in C. crescentus der Zusammenbau der Geissel, der Fimbrien und der Oberflächenmatrix (Kapsel) in genau vorprogrammierten Phasen des Zellzyklus geschieht. Durch unsere Vorarbeiten erhielten vor kurzen wichtige Hinweise dafür, dass die Untereinheiten der Geissel (auch Flagellum genannt) und/oder für die Produktion der Kapsel durch Sialinsäure-Zuckerresten verknüpft werden und dass, sich der Zusammenbau der Fimbrien und der Geissel durch spezielle Eiweisse erfolgt, die sich am Zellpol befinden, einer Zellzykluskontrolle unterliegen und dadurch den Zusammenbau mehrerer Oberflächenstrukturen koordiniert. Mit diesem Projekt wird nicht nur die Grundlagenforschung in einem harmlosen Modellbakterium gefördert, sondern auch neue wichtige Erkenntnisse geschaffen, die als Angriffspunkt zur möglichen Bekämpfung krankheitserregender Bakterien dienen könnten, da die Geissel, Fimbrien und die Kapsel im Allgemeinen wichtige Virulenzfaktoren darstellen, die man mittels gezielter Inaktivierung ausschalten kann, um so bakterielle Infektionen zu reduzieren oder zu verhindern.

Direct link to Lay Summary Last update: 02.10.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Biology of Chlamydia
Klöckner Anna, Bühl Henrike, Viollier Patrick, Henrichfreise Beate (2018), Biology of Chlamydia, Springer International Publishing, Cham.
End-in-Sight: Cell Polarization by the Polygamic Organizer PopZ
Bergé Matthieu, Viollier Patrick H. (2018), End-in-Sight: Cell Polarization by the Polygamic Organizer PopZ, in Trends in Microbiology, 26(4), 363-375.
More than a Tad: spatiotemporal control of Caulobacter pili
Mignolet Johann, Panis Gaël, Viollier Patrick H (2018), More than a Tad: spatiotemporal control of Caulobacter pili, in Current Opinion in Microbiology, 42, 79-86.
Peptidoglycan in obligate intracellular bacteriaPeptidoglycan in obligate intracellular bacteria
Otten Christian, Brilli Matteo, Vollmer Waldemar, Viollier Patrick H., Salje Jeanne (2018), Peptidoglycan in obligate intracellular bacteriaPeptidoglycan in obligate intracellular bacteria, in Molecular Microbiology, 107(2), 142-163.
A novel nucleoid-associated protein coordinates chromosome replication and chromosome partition
Taylor James A., Panis Gaël, Viollier Patrick H., Marczynski Gregory T. (2017), A novel nucleoid-associated protein coordinates chromosome replication and chromosome partition, in Nucleic Acids Research, 45(15), 8916-8929.
Hit the right spots: cell cycle control by phosphorylated guanosines in alphaproteobacteria
Hallez Régis, Delaby Marie, Sanselicio Stefano, Viollier Patrick H. (2017), Hit the right spots: cell cycle control by phosphorylated guanosines in alphaproteobacteria, in Nature Reviews Microbiology, 15(3), 137-148.
Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator
Mignolet Johann, Holden Seamus, Bergé Matthieu, Panis Gaël, Eroglu Ezgi, Théraulaz Laurence, Manley Suliana, Viollier Patrick H (2016), Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator, in eLife, 5, 1-21.
Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria
Bergé Matthieu, Campagne Sébastien, Mignolet Johann, Holden Seamus, Théraulaz Laurence, Manley Suliana, Allain Frédéric H-T, Viollier Patrick H (2016), Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria, in eLife, 5, 1-31.
Cell Cycle Constraints and Environmental Control of Local DNA Hypomethylation in α-Proteobacteria
Ardissone Silvia, Redder Peter, Russo Giancarlo, Frandi Antonio, Fumeaux Coralie, Patrignani Andrea, Schlapbach Ralph, Falquet Laurent, Viollier Patrick H. (2016), Cell Cycle Constraints and Environmental Control of Local DNA Hypomethylation in α-Proteobacteria, in PLOS Genetics, 12(12), e1006499-e1006499.
In-phase oscillation of global regulons is orchestrated by a pole-specific organizer
Janakiraman Balaganesh, Mignolet Johann, Narayanan Sharath, Viollier Patrick H., Radhakrishnan Sunish Kumar (2016), In-phase oscillation of global regulons is orchestrated by a pole-specific organizer, in Proceedings of the National Academy of Sciences, 113(44), 12550-12555.
Growth control switch by a DNA-damage-inducible toxin–antitoxin system in Caulobacter crescentus
Kirkpatrick Clare L., Martins Daniel, Redder Peter, Frandi Antonio, Mignolet Johann, Chapalay Julien Bortoli, Chambon Marc, Turcatti Gerardo, Viollier Patrick H. (2016), Growth control switch by a DNA-damage-inducible toxin–antitoxin system in Caulobacter crescentus, in Nature Microbiology, 1(4), 16008-16008.
Convergence of Alarmone and Cell Cycle Signaling from Trans -Encoded Sensory Domains
Sanselicio Stefano, Viollier Patrick H. (2015), Convergence of Alarmone and Cell Cycle Signaling from Trans -Encoded Sensory Domains, in mBio, 6(5), 1-10.
An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle
Joshi Kamal Kishore, Bergé Matthieu, Radhakrishnan Sunish Kumar, Viollier Patrick Henri, Chien Peter (2015), An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle, in Cell, 163(2), 419-431.

Associated projects

Number Title Start Funding scheme
160703 Pangenomic and comprehensive analysis of the relationship between bacterial toxin-antitoxin systems and antibiotic phenotype 01.12.2015 Sinergia
177127 Real-time super resolution microscopy for microbial cell biology in 4D 01.05.2018 R'EQUIP
182576 Cell cycle-regulated surface structures and mobile DNA in bacteria 01.10.2018 Project funding (Div. I-III)
143660 Regulatory interplay of cell cycle transcription factors in compartmentalized Caulobacter cells 01.10.2012 Project funding (Div. I-III)

Abstract

Cells typically implement a myriad of molecular and macromolecular changes during cell cycle progression. The remodeling of cell surface structures and proteinaceous appendages during the bacterial cell cycle is still poorly understood. Arguably the best model system in which to study such structures and the underlying mechanism is the synchronizable a-proteobacterium Caulobacter crescentus (henceforth Caulobacter). This Gram-negative aquatic bacterium is non-pathogenic, but it divides asymmetrically and it features several surface structures whose functions can be conveniently probed using forward genetics. The power of such genetics alerted us to study new fundamental mechanisms and functions of three cell cycle-regulated structures: the polar flagellum, the polar pili and the capsule that are present at different times during the cell cycle. Our specific goals, framed in three ambitious and unrelated aims, are to:1) Explore how protein glycosylation controls flagellum assembly in Caulobacter via glycosyltransferase orthologs. 2) Dissect the cell polarization pathway that acts on pili.We will reconstitute the MapX/P polarization pathway and determine which known (or potentially unknown) pilus proteins are targeted by MapX/P in Caulobacter. 3) Use chemical-genetics to probe the protective functions of the capsule. We will screen for inhibitors of capsule production in an FDA-approved small molecule library and we will determine the genetic basis for the protection of the capsule from bacteriophages.Our studies on three cell cycle-regulated surface structures and the underlying mechanisms are important because they address fundamental concepts in eukaryotic and bacterial cell biology, including how protein function is regulated by glycosylation, how cell polarization is achieved and how exopolysaccharides fulfill protective roles. Additionally, these topics are of medical relevance as flagellin glycosylation, piliation and/or capsulation are required for virulence in many bacterial pathogens and many cousins of Caulobacter are plant, animal and/or human pathogens that also divide asymmetrically. Lastly compound screening experiments proposed here with Caulobacter make major strides in antibacterial drug discovery and may set the stage for a new combinatorial screening strategy.
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