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Resistance of Yersinia pestis to complement-dependent killing is mediated by the Ail outer membrane protein
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). (Hans Wolf-Watz)
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2008 (Engelska)Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 76, nr 2, s. 612-622Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Yersinia pestis, the causative agent of plague, must survive in blood in order to cause disease and to be transmitted from host to host by fleas. Members of the Ail/Lom family of outer membrane proteins provide protection from complement-dependent killing for a number of pathogenic bacteria. The Y. pestis KIM genome is predicted to encode four Ail/Lom family proteins. Y. pestis mutants specifically deficient in expression of each of these proteins were constructed using lambda Red-mediated recombination. The Ail outer membrane protein was essential for Y. pestis to resist complement-mediated killing at 26 and 37 degrees C. Ail was expressed at high levels at both 26 and 37 degrees C, but not at 6 degrees C. Expression of Ail in Escherichia coli provided protection from the bactericidal activity of complement. High-level expression of the three other Y. pestis Ail/Lom family proteins (the y1682, y2034, and y2446 proteins) provided no protection against complement-mediated bacterial killing. A Y. pestis ail deletion mutant was rapidly killed by sera obtained from all mammals tested except mouse serum. The role of Ail in infection of mice, Caenorhabditis elegans, and fleas was investigated.

Ort, förlag, år, upplaga, sidor
2008. Vol. 76, nr 2, s. 612-622
Identifikatorer
URN: urn:nbn:se:umu:diva-33949DOI: 10.1128/IAI.01125-07PubMedID: 18025094OAI: oai:DiVA.org:umu-33949DiVA, id: diva2:318869
Tillgänglig från: 2010-05-11 Skapad: 2010-05-11 Senast uppdaterad: 2018-03-15Bibliografiskt granskad
Ingår i avhandling
1. Outer membrane proteins of Yersinia pestis: Ail and OmpA
Öppna denna publikation i ny flik eller fönster >>Outer membrane proteins of Yersinia pestis: Ail and OmpA
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), Umeå universitet, 2010. s. 89
Serie
Doctoral thesis / Umeå University, Department of Molecular Biology
Nyckelord
Yersinia pestis, outer membrane proteins, Ail, ompA
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Forskningsämne
immunologi; mikrobiologi; infektionssjukdomar
Identifikatorer
urn:nbn:se:umu:diva-33956 (URN)978-91-7459-030-2 (ISBN)
Disputation
2010-06-03, Molekylärbiologi, Major Groove, Byggnad 6L, Umeå universitet, Umeå, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2010-05-12 Skapad: 2010-05-11 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

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