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Yersinia pestis kills Caenorhabditis elegans by a biofilm-independent process that involves novel virulence factors.
3Department of Microbiology & Immunology, University of Miami School of Medicine, Miami, Florida, USA.
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2005 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 6, no 10, 992-997 p.Article in journal (Refereed) Published
Abstract [en]

It is known that Yersinia pestis kills Caenorhabditis elegans by a biofilm-dependent mechanism that is similar to the mechanism used by the pathogen to block food intake in the flea vector. Using Y. pestis KIM 5, which lacks the genes that are required for biofilm formation, we show that Y. pestis can kill C. elegans by a biofilm-independent mechanism that correlates with the accumulation of the pathogen in the intestine. We used this novel Y. pestis-C. elegans pathogenesis system to show that previously known and unknown virulence-related genes are required for full virulence in C. elegans. Six Y. pestis mutants with insertions in genes that are not related to virulence before were isolated using C. elegans. One of the six mutants carried an insertion in a novel virulence gene and showed significantly reduced virulence in a mouse model of Y. pestis pathogenesis. Our results indicate that the Y. pestis-C. elegans pathogenesis system that is described here can be used to identify and study previously uncharacterized Y. pestis gene products required for virulence in mammalian systems.

Place, publisher, year, edition, pages
2005. Vol. 6, no 10, 992-997 p.
URN: urn:nbn:se:umu:diva-33951DOI: 10.1038/sj.embor.7400516PubMedID: 16170309OAI: diva2:318871
Available from: 2010-05-11 Created: 2010-05-11 Last updated: 2010-05-12
In thesis
1. Outer membrane proteins of Yersinia pestis: Ail and OmpA
Open this publication in new window or tab >>Outer membrane proteins of Yersinia pestis: Ail and OmpA
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A vast number of studies have been completed on the virulence determinants of Yersinia spp.; however, the focus of many of these studies has been on the virulence plasmid and the plasmid-encoded Type three secretion system. Nevertheless, many chromosomal genes whose products are directly involved in virulence have also been identified. Some of these critical virulence determinants are outer membrane proteins. Outer membrane proteins of Gram-negative bacteria often have important physiological roles; however, some have also been found to be important for pathogenesis. In this thesis, we investigated two Yersinia. pestis outer membrane proteins, Ail and OmpA, and their roles in virulence. We provide evidence that Y. pestis Ail is a highly expressed outer membrane protein that is absolutely essential for Y. pestis to resist the killing action of the complement system present in human blood and tissues, as well as the blood and tissues of other mammalian hosts. Furthermore, Ail was important for virulence in a Y. pestis-Canorhabditis elegans model of infection.The work in this thesis also provided the first evidence that another surface-exposed outer membrane protein, termed OmpA, is required for both Yersinia pseudotuberculosis and Y. pestis to survive and proliferate intracellularly in macrophages. Finally, we provide evidence that Y. pestis has a functional small RNA MicA that controls the expression of OmpA. This is the first demonstration of sRNA-mediated regulation of a Yersinia virulence factor. This work has paved the way for future studies on the role of outer membrane proteins in virulence, particularly the role of Ail and OmpA.

Place, publisher, year, edition, pages
Umeå: Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), Umeå universitet, 2010. 89 p.
Doctoral thesis / Umeå University, Department of Molecular Biology
Yersinia pestis, outer membrane proteins, Ail, ompA
National Category
Microbiology in the medical area
Research subject
Immunology; Microbiology; Infectious Diseases
urn:nbn:se:umu:diva-33956 (URN)978-91-7459-030-2 (ISBN)
Public defence
2010-06-03, Molekylärbiologi, Major Groove, Byggnad 6L, Umeå universitet, Umeå, 10:00 (English)
Available from: 2010-05-12 Created: 2010-05-11 Last updated: 2010-05-18Bibliographically approved

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