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| Article Authors: | Fadel Sayes; Lin Sun; Mariagrazia Di Luca; Roxane Simeone; Nathalie Degaiffier; Laurence Fiette; Semih Esin; Roland Brosch; Daria Bottai; Claude Leclerc; Laleh Majlessi |
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| Article Title: | Strong Immunogenicity and Cross-Reactivity of Mycobacterium tuberculosis ESX-5 Type VII Secretion -Encoded PE-PPE Proteins Predicts Vaccine Potential. |
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| Reference ID: | 1023051 |
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| Abstract: | The genome of Mycobacterium tuberculosis (Mtb) encodes five type VII secretion systems, ESX-1 to ESX-5, most of which are associated with genes encoding PE/PPE proteins, named after their N-terminal Pro-Glu (PE) or Pro-Pro-Glu (PPE) motifs. Here, we describe the strong T cell immunogenicity of the ESX-5-encoded PE/PPE proteins, which share a large panel of cross-reactive CD4(+) epitopes with substantial numbers of their ESX-5-nonassociated PE/PPE homologs. The immunogenicity of these numerous PE/PPE proteins is dependent on their export by a functional EccD(5), the predicted transmembrane channel of the ESX-5 secretion apparatus. The Mtb ppe25-pe19 mutant deleted for all ESX-5-associated pe and ppe genes, although highly attenuated in immunocompetent mice, remains able to induce immunity against the ESX-5-associated PE/PPE virulence factors, via cross-reactivity with their numerous homologs, and against the ESX-1 virulence factors ESAT-6/CFP-10. The ppe25-pe19 strain is strongly protective against Mtb infection in mice and represents a potential antituberculosis vaccine candidate. |
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| Affiliations: | Unité de Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris F-75015, France; INSERM U1041, Paris F-75015, France. |
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| Date: | 2012 |
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| Reference Type: | Literature |
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| PubMed ID: | 22520463 |
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| Journal: | Cell Host Microbe |
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| Journal Volume: | 11 |
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| Article Pages: | 352-63 |
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| Journal ISSN: | 1934-6069 |
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| Curation Last Updated: | 2013-05-28 22:41:28 |
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