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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 universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Department of Medical Countermeasures, Division of NBC-Defense, Swedish Defense Research Agency.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
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2002 (Engelska)Ingår i: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 184, nr 16, s. 4500-4509Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
American Society for Microbiology , 2002. Vol. 184, nr 16, s. 4500-4509
Nationell ämneskategori
Mikrobiologi inom det medicinska området Biokemi och molekylärbiologi
Identifikatorer
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
Tillgänglig från: 2005-10-27 Skapad: 2005-10-27 Senast uppdaterad: 2019-01-23Bibliografiskt granskad
Ingår i avhandling
1. Virulence mechanisms of pathogenic Yersinia: aspects of type III secretion and twin arginine translocation
Öppna denna publikation i ny flik eller fönster >>Virulence mechanisms of pathogenic Yersinia: aspects of type III secretion and twin arginine translocation
2005 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2005. s. 67
Nyckelord
Molecular biology, Yersinia pestis, Yersinia pseudotuberculosis, bacterial pathogenesis, type III secretion, twin arginine translocation, virulence mechanisms, YscU, YscP, YscF, Molekylärbiologi
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-619 (URN)91-7305-948-X (ISBN)
Disputation
2005-11-25, Lecture Hall "Major Groove", 6L, NUS, Umeå Universitet, 901 87 Umeå, 10:00
Opponent
Handledare
Tillgänglig från: 2005-10-27 Skapad: 2005-10-27 Senast uppdaterad: 2019-01-24Bibliografiskt granskad

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

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Lavander, MoaSundberg, LenaEdqvist, PetraWolf-Watz, HansForsberg, Åke
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Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)Institutionen för molekylärbiologi (Medicinska fakulteten)
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