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Type III secretion translocon assemblies that attenuate Yersinia virulence
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Matthew Francis)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Matthew Francis)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). (Matthew Francis)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). (Hans Wolf-Watz)
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2013 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 7, 1088-1110 p.Article in journal (Refereed) Published
Abstract [en]

Type III secretion enables bacteria to intoxicate eukaryotic cells with anti-host effectors. A class of secreted cargo are the two hydrophobic translocators that form a translocon pore in the host cell plasma membrane through which the translocated effectors may gain cellular entry. In pathogenic Yersinia, YopB and YopD shape this translocon pore. Here, four in cis yopD mutations were constructed to disrupt a predicted α-helix motif at the C-terminus. Mutants YopD(I262P) and YopD(K267P) poorly localized Yop effectors into target eukaryotic cells and failed to resist uptake and killing by immune cells. These defects were due to deficiencies in host-membrane insertion of the YopD-YopB translocon. Mutants YopD(A263P) and YopD(A270P) had no measurable in vitro translocation defect, even though they formed smaller translocon pores in erythrocyte membranes. Despite this, all four mutants were attenuated in a mouse infection model. Hence, YopD variants have been generated that can spawn translocons capable of targeting effectors in vitro, yet were bereft of any lethal effect in vivo. Therefore, Yop translocators may possess other in vivo functions that extend beyond being a portal for effector delivery into host cells.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013. Vol. 15, no 7, 1088-1110 p.
Keyword [en]
virulence, coiled-coil, effector delivery, pore formation, regulation, YopD
National Category
Microbiology Biochemistry and Molecular Biology Microbiology in the medical area
Research subject
Infectious Diseases; Microbiology; Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-67117DOI: 10.1111/cmi.12100ISI: 000320394800004OAI: oai:DiVA.org:umu-67117DiVA: diva2:610817
Funder
Swedish Research Council
Note

This work, performed within the framework of the Umea Centre for Microbial Research-Linnaeus Program, was supported by grants from the Carl Tryggers Foundation for Scientific Research (M. S. F.), Swedish Research Council (H.W.-W., M. F., T. E., M. S. F.), Foundation for Medical Research at Umea University (M. S. F.) and J C Kempe Memorial Fund (T. R. C., A. A. A.).

Available from: 2013-03-13 Created: 2013-03-13 Last updated: 2017-12-06Bibliographically approved

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Costa, TiagoAmer, AyadFarag, SalahWolf-Watz, HansFällman, MariaFahlgren, AnnaEdgren, TomasFrancis, Matthew

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Costa, TiagoAmer, AyadFarag, SalahWolf-Watz, HansFällman, MariaFahlgren, AnnaEdgren, TomasFrancis, Matthew
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Department of Molecular Biology (Faculty of Science and Technology)Umeå Centre for Microbial Research (UCMR)Molecular Infection Medicine Sweden (MIMS)Department of Molecular Biology (Faculty of Medicine)
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Cellular Microbiology
MicrobiologyBiochemistry and Molecular BiologyMicrobiology in the medical area

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