近日,，法國(guó)和意大利研究人員發(fā)現(xiàn)與導(dǎo)致結(jié)核病的結(jié)核分枝桿菌(結(jié)核桿菌)毒性有關(guān)的蛋白質(zhì),，并成功培育出其活性減毒突變體,，有望在將來(lái)研發(fā)出比卡介苗更有效的結(jié)核病疫苗,。
法國(guó)巴斯德研究所,、法國(guó)國(guó)家衛(wèi)生與醫(yī)學(xué)研究所和意大利比薩大學(xué)的研究人員通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，改變結(jié)核桿菌的ESX-5基因組,，可阻斷PE/PPE蛋白的生產(chǎn)與運(yùn)輸。實(shí)驗(yàn)結(jié)果表明,，感染變異結(jié)核桿菌的小鼠并不會(huì)患上結(jié)核病,，這證明PE/PPE蛋白是影響結(jié)核桿菌毒性的重要因素之一。研究人員還發(fā)現(xiàn),，感染變異結(jié)核桿菌的小鼠對(duì)結(jié)核桿菌產(chǎn)生了抗體,，這表明人們可利用結(jié)核桿菌的該活性減毒突變體研發(fā)出更有效的結(jié)核病疫苗。
研究人員表示,，下一步目標(biāo)是尋找一種對(duì)人類無(wú)害的變異基因組,。
結(jié)核病由結(jié)核桿菌引起，是世界上傳播最廣泛的疾病之一,，影響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.
