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Proteolytic Cleavage of the FlhB Homologue YscU of Yersinia pseudotuberculosis Is Essential for Bacterial Survival
Department of Medical Countermeasures, Division of NBC-Defense, Swedish Defense Research Agency.
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Medical Countermeasures, Division of NBC-Defense, Swedish Defense Research Agency.
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
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2002 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 184, no 16, p. 4500-4509Article in journal (Refereed) Published
Abstract [en]

Pathogenic Yersinia species employ a type III secretion system (TTSS) to target antihost factors, Yop proteins, into eukaryotic cells. The secretion machinery is constituted of ca. 20 Ysc proteins, nine of which show significant homology to components of the flagellar TTSS. A key event in flagellar assembly is the switch from secreting-assembling hook substrates to filament substrates, a switch regulated by FlhB and FliK. The focus of this study is the FlhB homologue YscU, a bacterial inner membrane protein with a large cytoplasmic C-terminal domain. Our results demonstrate that low levels of YscU were required for functional Yop secretion, whereas higher levels of YscU lowered both Yop secretion and expression. Like FlhB, YscU was cleaved into a 30-kDa N-terminal and a 10-kDa C-terminal part. Expression of the latter in a wild-type strain resulted in elevated Yop secretion. The site of cleavage was at a proline residue, within the strictly conserved amino acid sequence NPTH. A YscU protein with an in-frame deletion of NPTH was cleaved at a different position and was nonfunctional with respect to Yop secretion. Variants of YscU with single substitutions in the conserved NPTH sequence--i.e., N263A, P264A, or T265A--were not cleaved but retained function in Yop secretion. Elevated expression of these YscU variants did, however, result in severe growth inhibition. From this we conclude that YscU cleavage is not a prerequisite for Yop secretion but is rather required to maintain a nontoxic fold.

Place, publisher, year, edition, pages
American Society for Microbiology , 2002. Vol. 184, no 16, p. 4500-4509
National Category
Microbiology in the medical area Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-4777DOI: 10.1128/JB.184.16.4500-4509.2002ISI: 000177059500020PubMedID: 12142420OAI: oai:DiVA.org:umu-4777DiVA, id: diva2:144011
Available from: 2005-10-27 Created: 2005-10-27 Last updated: 2019-01-23Bibliographically approved
In thesis
1. Virulence mechanisms of pathogenic Yersinia: aspects of type III secretion and twin arginine translocation
Open this publication in new window or tab >>Virulence mechanisms of pathogenic Yersinia: aspects of type III secretion and twin arginine translocation
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The pathogenic bacteria Yersinia pestis and Y. pseudotuberculosis are related to the degree where the former is considered a subspecies of the latter, and still they cause disease of little resemblance in humans. Y. pestis is the causative agent of lethal bubonic and pneumonic plague, while Y. pseudotuberculosis manifests itself as mild gastroenteritis. An important virulence determinant for these species is their ability to secrete and inject toxins (Yop effectors) into immune cells of the infected host, in a bacterium-cell contact dependent manner. This ability depends on the extensively studied type III secretion system, a highly complex multicomponent structure resembling a needle. The induction of Yop secretion is a strictly controlled event. The two structural type III secretion components YscU and YscP are here shown to play a crucial role in this process, which is suggested to require an YscP mediated conformational change of the C-terminus of YscU. Proteolytic cleavage of YscU within this domain is further revealed to be a prerequisite for functional Yop secretion. The needle subcomponent itself, YscF, is recognised as a regulatory element that controls the induction of Yop effectors and their polarised delivery into target cells. Potentially, the needle might act as a sensor that transmits the inducing signal (i.e. target cell contact) to activate the type III secretion system. Secondly a, for Yersinia, previously unexplored system, the Twin arginine translocation (Tat) pathway, is shown to be functional and absolutely required for virulence of Y. pseudotuberculosis. A range of putative Yersinia Tat substrates were predicted in silico, which together with the Tat system itself may be interesting targets for future development of antimicrobial treatments.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2005. p. 67
Keywords
Molecular biology, Yersinia pestis, Yersinia pseudotuberculosis, bacterial pathogenesis, type III secretion, twin arginine translocation, virulence mechanisms, YscU, YscP, YscF, Molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-619 (URN)91-7305-948-X (ISBN)
Public defence
2005-11-25, Lecture Hall "Major Groove", 6L, NUS, Umeå Universitet, 901 87 Umeå, 10:00
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Available from: 2005-10-27 Created: 2005-10-27 Last updated: 2019-01-24Bibliographically approved

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Lavander, MoaSundberg, LenaEdqvist, PetraWolf-Watz, HansForsberg, Åke
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