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Delivery of TypeIII Secreted Toxins by Yersinia pseudotuberculosis: the Role of LcrV, YopD, and Free Lipids in the Translocation Process
Umeå University, Faculty of Medicine, Molecular Biology.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacteria that infect humans and animals face a hard combat with the host´s immune system and in order to establish infection, pathogenic bacteria has evolved mechanisms to avoid being cleared from the host tissue. Many Gram-negatives carry a Type 3 secretion (T3S) system that is used to deliver effector proteins (toxins) into host cells. The toxins exhibit a broad range of intra cellular effects that has in common that they increase the chances of the bacteria to establish infection, multiply in infected tissue or spread to other tissues or hosts. The object of this study was to analyse the mechanisms behind the T3S effectors delivery into target cells. Two bacterial proteins, LcrV and YopD, which are involved in the translocation of effectors were analyzed by mutagenesis. LcrV was found to affect the efficiency of the translocation, probably by determining the size of the pore in the target cell membrane through which the effectors pass. Truncated variants of the multi-functional YopD revealed that defined regions of the protein were important for pore-formation and translocation. Effectors and translocators were demonstrated to form complexes with free acyl chains (lipids) at the bacterial surface. These complexes –termed Yop-lipid complexes, (YLC)– are released from the surface and can act as discrete units that are able to promote translocation of effectors even when separated from the bacterium from which they originate. These findings shed new light on the process of effector translocation by Yersinia and possibly by other gram-negative bacterial pathogens with a similar T3S setup.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi (Teknisk-naturvetenskaplig fakultet) , 2006. , 60 p.
Keyword [en]
Yersinia, T3SS, translocation, YopD, LcrV, YLC, fatty acids.
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-800ISBN: 91-7264-092-8 (print)OAI: oai:DiVA.org:umu-800DiVA: diva2:144594
Public defence
2006-06-02, major groove, 6L, NUS, 901 87, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2006-05-11 Created: 2006-05-11 Last updated: 2009-10-27Bibliographically approved
List of papers
1. LcrV is a channel size-determining component of the Yop effector translocon of Yersinia
Open this publication in new window or tab >>LcrV is a channel size-determining component of the Yop effector translocon of Yersinia
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2001 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 39, no 3, 620-632 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5180 (URN)10.1046/j.1365-2958.2001.02259.x (DOI)11169103 (PubMedID)
Available from: 2006-05-11 Created: 2006-05-11 Last updated: 2012-03-09Bibliographically approved
2. The YopD translocator of Yersinia pseudotuberculosis is a multifunctional protein comprised of discrete domains.
Open this publication in new window or tab >>The YopD translocator of Yersinia pseudotuberculosis is a multifunctional protein comprised of discrete domains.
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2004 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 186, no 13, 4110-4123 p.Article in journal (Refereed) Published
Abstract [en]

To establish an infection, Yersinia pseudotuberculosis utilizes a plasmid-encoded type III translocon to microinject several anti-host Yop effectors into the cytosol of target eukaryotic cells. YopD has been implicated in several key steps during Yop effector translocation, including maintenance of yop regulatory control and pore formation in the target cell membrane through which effectors traverse. These functions are mediated, in part, by an interaction with the cognate chaperone, LcrH. To gain insight into the complex molecular mechanisms of YopD function, we performed a systematic mutagenesis study to search for discrete functional domains. We highlighted amino acids beyond the first three N-terminal residues that are dispensable for YopD secretion and confirmed that an interaction between YopD and LcrH is essential for maintenance of yop regulatory control. In addition, discrete domains within YopD that are essential for both pore formation and translocation of Yop effectors were identified. Significantly, other domains were found to be important for effector microinjection but not for pore formation. Therefore, YopD is clearly essential for several discrete steps during efficient Yop effector translocation. Recognition of this modular YopD domain structure provides important insights into the function of YopD.

Keyword
Bacterial Outer Membrane Proteins/chemistry/*physiology, Bacterial Proteins/physiology, Base Sequence, Hela Cells, Hemolysis, Humans, Molecular Chaperones/physiology, Molecular Sequence Data, Protein Transport, Yersinia pseudotuberculosis/*physiology
Identifiers
urn:nbn:se:umu:diva-16673 (URN)10.1128/JB.186.13.4110-4123.2004 (DOI)15205412 (PubMedID)
Available from: 2007-10-08 Created: 2007-10-08 Last updated: 2010-04-22Bibliographically approved
3. Translocation of virulence determinants is mediated by a surface located protein-lipid complex.
Open this publication in new window or tab >>Translocation of virulence determinants is mediated by a surface located protein-lipid complex.
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Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-5182 (URN)
Available from: 2006-05-11 Created: 2006-05-11 Last updated: 2010-01-13Bibliographically approved

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Citation style
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