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Cell-to-cell communication and virulence in Vibrio anguillarum
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Debra Milton)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Quorum sensing (QS) is a type of cell-to-cell communication that allows the bacteria to communicate via small molecules to coordinate activities such as growth, biofilm formation, virulence, and stress response as a population. QS depends on the accumulation of signal molecules as the bacterial population increases. After a critical threshold of the signal molecules are reached, the bacteria induce a cellular response allowing the bacteria to coordinate their activities as a population.

In Vibrio anguillarum, three parallel quorum-sensing phosphorelay systems channels information via three hybrid sensor kinases VanN, VanQ, and CqsS that function as receptors for signal molecules produced by the synthases VanM, VanS, and CqsA, respectively. The phosphorelay systems converge onto a single regulatory pathway via the phosphotransferase VanU, which phosphorylates the response regulator VanO. Together with the alternative sigma factor RpoN, VanO activates the expression of a small RNA, Qrr1 (Quorum regulatory RNA), which in conjunction with the small RNA chaperone Hfq, destabilizes vanT mRNA, which encode the major quorum-sensing regulator in V. anguillarum. This thesis furthers the knowledge on the quorum-sensing phosphorelay systems in V. anguillarum.

In this study, three additional qrr genes were identified, which were expressed during late logarithmic growth phase. The signal synthase VanM activated the expression of the Qrr1-4, which stands in contrast to Qrr regulation in other vibrios. Moreover, in addition to VanO, we predict the presence of a second response regulator which can be phosphorylated by VanU and repress Qrr1-4 expression. Thus, VanU functions as a branch point that can regulate the quorum-sensing regulon by activating or repressing VanT expression. Furthermore, VanT was shown to directly activate VanM expression and thus forming a negative regulatory loop, in which VanM represses VanT expression indirectly via Qrr1-4. In addition, VanM expression was negatively regulated post-transcriptionally by Hfq. Furthermore, a universal stress protein UspA repressed VanM expression via the repression of VanT expression. We showed that UspA binds Hfq, thus we suggest that UspA plays a role in sequestering Hfq and indirectly affect gene expression.

This thesis also investigated the mechanism by which V. anguillarum can attach to and colonize fish skin tissue. We show unequivocally that fish skin epithelial cells can internalize bacteria, thus keeping the skin clear from pathogens. In turn, V. anguillarum utilized the lipopolysaccharide O-antigen to evade internalization by the fish skin epithelial cells. This study provides new insights into the molecular mechanism by which pathogen interacts with marine animals to cause disease.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2012. , 59 p.
Keyword [en]
vibrio anguillarum, quorum sensing, stress response, keratocyte
National Category
Research subject
Molecular Biology
URN: urn:nbn:se:umu:diva-54356ISBN: 978-91-7459-427-0OAI: diva2:517616
Public defence
2012-05-22, NUS 6A–L - Biomedicinhuset, Major groove, Umeå universitet, Umeå, 09:00 (English)
Available from: 2012-04-27 Created: 2012-04-24 Last updated: 2012-05-02Bibliographically approved
List of papers
1. The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum
Open this publication in new window or tab >>The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum
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2011 (English)In: Microbiology, ISSN 1350-0872, E-ISSN 1465-2080, Vol. 157, no 12, 3324-3339 p.Article in journal (Refereed) Published
Abstract [en]

Vibrio anguillarum utilizes quorum sensing to regulate stress responses required for survival in the aquatic environment. Like other Vibrio species, V. anguillarum contains the gene qui, which encodes the ancestral quorum regulatory RNA Owl, and phosphorelay quorum-sensing systems that modulate the expression of small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional regulator VanT. In this study, three additional Orr sRNAs were identified. All four sRNAs were positively regulated by sigma(54) and the sigma(54)-dependent response regulator Van, and showed a redundant activity. The Orr sRNAs, together with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at high cell density, and exogenously added N-acylhomoserine lactone molecules induced expression of the qrr genes at low cell density. The phosphotransferase VanU, which phosphorylates and activates VanO, repressed expression of the Orr sRNAs and stabilized van T mRNA. A model is presented proposing that VanU acts as a branch point, aiding cross-regulation between two independent phosphorelay systems that activate or repress expression of the Orr sRNAs, giving flexibility and precision in modulating VanT expression and inducing a quorum-sensing response to stresses found in a constantly changing aquatic environment.

Place, publisher, year, edition, pages
Society for General Microbiology, 2011
2-component signal-transduction; small rna regulators; response regulators; harveyi; phosphorelay; virulence; cholerae; metalloprotease; homolog; system
National Category
Microbiology in the medical area
urn:nbn:se:umu:diva-51489 (URN)10.1099/mic.0.051011-0 (DOI)000298520500009 ()
Available from: 2012-01-23 Created: 2012-01-23 Last updated: 2012-05-31Bibliographically approved

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