近日，法国和意大利研究人员发现与导致结核病的结核分枝杆菌(结核杆菌)毒性有关的蛋白质，并成功培育出其活性减毒突变体，有望在将来研发出比卡介苗更有效的结核病疫苗。
法国巴斯德研究所、法国国家卫生与医学研究所和意大利比萨大学的研究人员通过动物实验发现，改变结核杆菌的ESX-5基因组，可阻断PE/PPE蛋白的生产与运输。实验结果表明，感染变异结核杆菌的小鼠并不会患上结核病，这证明PE/PPE蛋白是影响结核杆菌毒性的重要因素之一。研究人员还发现，感染变异结核杆菌的小鼠对结核杆菌产生了抗体，这表明人们可利用结核杆菌的该活性减毒突变体研发出更有效的结核病疫苗。
研究人员表示，下一步目标是寻找一种对人类无害的变异基因组。
结核病由结核杆菌引起，是世界上传播最广泛的疾病之一，影响到世界上三分之一的人口。(生物谷：Bioon.com)
doi:10.1016/j.chom.2012.03.003
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PMID:
Strong Immunogenicity and Cross-Reactivity of Mycobacterium tuberculosis ESX-5 Type VII Secretion -Encoded PE-PPE Proteins Predicts Vaccine Potential
Fadel Sayes, Lin Sun, Mariagrazia Di Luca, Roxane Simeone, Nathalie Degaiffier, Laurence Fiette, Semih Esin, Roland Brosch, Daria Bottai, Claude Leclerc, Laleh Majlessi
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 EccD5, the predicted transmembrane channel of the ESX-5 secretion apparatus. The Mtb Δppe25-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 Δppe25-pe19 strain is strongly protective against Mtb infection in mice and represents a potential antituberculosis vaccine candidate.
