A calcium-responsive kinase induces the acute-to-chronic lifestyle switch in "Pseudomonas aeruginosa".
PhD Thesis, University of Basel,
Faculty of Science.
Restricted to Repository staff only until 1 March 2018.
Available under License CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives).
Official URL: http://edoc.unibas.ch/diss/DissB_11660
Virulence of pathogenic bacteria is a highly controlled process to facilitate invasion and survival in host tissues. While many of the regulatory pathways controlling virulence behavior have been defined in detail, information about host signals modulating these processes is still scarce. The opportunistic pathogen Pseudomonas aeruginosa causes acute and chronic infections in humans and is the leading cause of morbidity in cystic fibrosis (CF) patients. Disease progression is typically associated with the loss of acute virulence and the emergence of biofilms and chronic behavior. This acute-to-chronic switch is governed by the global Gac/Rsm pathway, which assembles around the central Gac two-component system and several associated sensor histidine kinases. The signal(s) and mechanisms involved in Gac/Rsm activation and induction of chronic behavior are not known. Using a newly developed Gac/Rsm-responsive dual reporter system we show that calcium stimulates the signaling cascade via the action of the Gac-associated hybrid histidine kinase LadS. Specific activation of LadS by calcium ions depends on its histidine kinase activity and on the periplasmic DISMED2 sensor domain. Our data suggest that calcium sensing by LadS evolved as an adaptation to the opportunistic behavior of P. aeruginosa. Consistent with a role for LadS in chronic infections, most clinical isolates from CF airways remain calcium-responsive during decades of evolution in the human host. We propose that elevated calcium levels in host tissue acts as trigger to induce the acute-to-chronic virulence switch during persistent P. aeruginosa infections. By establishing calcium signaling in host-pathogen interaction these results add to a growing body of evidence indicating that calcium signaling plays an important role not only in eukaryotic but also in prokaryotic cells.
|Advisors:||Jenal, Urs and Basler, Marek|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (xii, 108 Seiten)|
|Last Modified:||30 Jun 2016 11:01|
|Deposited On:||23 May 2016 07:31|
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