Vaccination of Mice with a Yop Translocon Complex Elicits Antibodies That Are Protective against Infection with F1
            <sup>−</sup>
            <i>Yersinia pestis</i>

Ivanov, Maya I.; Noel, Betty L.; Rampersaud, Ryan; Mena, Patricio; Benach, Jorge L.; Bliska, James B.

doi:10.1128/iai.00189-08

Cited by 42 publications

(47 citation statements)

References 53 publications

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“…In addition, other investigators (28) have succeeded in isolating extracellular YopBDE complexes from the supernatant of Yersinia pestis cultures in which the bacteria had been induced to secrete effector proteins. Vaccination of mice with these complexes induced protective immunity against Y. pestis strains lacking the F1 capsid, which suggests that the complexes are exposed and recognized by the humoral immune system in the absence of the protective extracellular capsid (28). A recent screen for small-molecule inhibitors of Yop translocation in Y. pseudotuberculosis also identified molecules that inhibit effector translocation but not Yop synthesis or secretion (29), which further supports a two-step mechanism for T3SS-dependent protein translocation in Yersinia.…”

Section: Discussionmentioning

confidence: 99%

Translocation of surface-localized effectors in type III secretion

Akopyan

Edgren

Wang-Edgren

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Pathogenic Yersinia species suppress the host immune response by using a plasmid-encoded type III secretion system (T3SS) to translocate virulence proteins into the cytosol of the target cells. T3SS-dependent protein translocation is believed to occur in one step from the bacterial cytosol to the target-cell cytoplasm through a conduit created by the T3SS upon target cell contact. Here, we report that T3SS substrates on the surface of Yersinia pseudotuberculosis are translocated into target cells. Upon host cell contact, purified YopH coated on Y. pseudotuberculosis was specifically and rapidly translocated across the target-cell membrane, which led to a physiological response in the infected cell. In addition, translocation of externally added YopH required a functional T3SS and a specific translocation domain in the effector protein. Efficient, T3SS-dependent translocation of purified YopH added in vitro was also observed when using coated Salmonella typhimurium strains, which implies that T3SS-mediated translocation of extracellular effector proteins is conserved among T3SS-dependent pathogens. Our results demonstrate that polarized T3SS-dependent translocation of proteins can be achieved through an intermediate extracellular step that can be reconstituted in vitro. These results indicate that translocation can occur by a different mechanism from the assumed single-step conduit model.

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Section: Discussionmentioning

confidence: 99%

Translocation of surface-localized effectors in type III secretion

Akopyan

Edgren

Wang-Edgren

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Anti-LcrV serum and control serum were obtained from LcrV-immunized or adjuvant-only injected mice, respectively, as described by Ivanov et al (18). The monoclonal antibody (MAb) specific for LcrV (MAb 7.3) has been described previously (17).…”

Section: Methodsmentioning

confidence: 99%

Yersinia pestisCan Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages

Noel

Lilo

Capurso

et al. 2009

Clin Vaccine Immunol

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“…Images are related by a rotation out of the page about the horizontal axis by ϳ90°to reveal two sides of the structure. (18,20,52) and LcrV (19). We demonstrated that GST-YopD wt (wild type) pulled down LcrH and/or YopB from Y. pseudotuberculosis-soluble lysates lacking endogenously produced YopD, YopB, LcrH, and LcrV (YPIII/pIB191) (supplemental Fig.…”

Section: Specific Loss Of Yop Regulatory Control In Some Amphipathicmentioning

confidence: 99%

YopD Self-assembly and Binding to LcrV Facilitate Type III Secretion Activity by Yersinia pseudotuberculosis

Costa

Edqvist

Bröms

et al. 2010

Journal of Biological Chemistry

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YopD-like translocator proteins encoded by several Gramnegative bacteria are important for type III secretion-dependent delivery of anti-host effectors into eukaryotic cells. This probably depends on their ability to form pores in the infected cell plasma membrane, through which effectors may gain access to the cell interior. In addition, Yersinia YopD is a negative regulator essential for the control of effector synthesis and secretion. As a prerequisite for this functional duality, YopD may need to establish molecular interactions with other key T3S components. A putative coiled-coil domain and an ␣-helical amphipathic domain, both situated in the YopD C terminus, may represent key protein-protein interaction domains. Therefore, residues within the YopD C terminus were systematically mutagenized. All 68 mutant bacteria were first screened in a variety of assays designed to identify individual residues essential for YopD function, possibly by providing the interaction interface for the docking of other T3S proteins. Mirroring the effect of a full-length yopD gene deletion, five mutant bacteria were defective for both yop regulatory control and effector delivery. Interestingly, all mutations clustered to hydrophobic amino acids of the amphipathic domain. Also situated within this domain, two additional mutants rendered YopD primarily defective in the control of Yop synthesis and secretion. Significantly, protein-protein interaction studies revealed that functionally compromised YopD variants were also defective in self-oligomerization and in the ability to engage another translocator protein, LcrV. Thus, the YopD amphipathic domain facilitates the formation of YopD/YopD and YopD/LcrV interactions, two critical events in the type III secretion process.

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Vaccination of Mice with a Yop Translocon Complex Elicits Antibodies That Are Protective against Infection with F1 ⁻ Yersinia pestis

Cited by 42 publications

References 53 publications

Translocation of surface-localized effectors in type III secretion

Translocation of surface-localized effectors in type III secretion

Yersinia pestisCan Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages

YopD Self-assembly and Binding to LcrV Facilitate Type III Secretion Activity by Yersinia pseudotuberculosis

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Vaccination of Mice with a Yop Translocon Complex Elicits Antibodies That Are Protective against Infection with F1 − Yersinia pestis

Cited by 42 publications

References 53 publications

Translocation of surface-localized effectors in type III secretion

Translocation of surface-localized effectors in type III secretion

Yersinia pestisCan Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages

YopD Self-assembly and Binding to LcrV Facilitate Type III Secretion Activity by Yersinia pseudotuberculosis

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Vaccination of Mice with a Yop Translocon Complex Elicits Antibodies That Are Protective against Infection with F1 ⁻ Yersinia pestis