LaRocque Regina C, Krastins Bryan, Harris Jason B, Lebrun Lauren M, Parker Kenneth C, Chase Michael, Ryan Edward T, Qadri Firdausi, Sarracino David, Calderwood Stephen B
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Infect Immun. 2008 Sep;76(9):4145-51. doi: 10.1128/IAI.00585-08. Epub 2008 Jun 30.
An effective vaccine for Vibrio cholerae is not yet available for use in the developing world, where the burden of cholera disease is highest. Characterizing the proteins that are expressed by V. cholerae in the human host environment may provide insight into the pathogenesis of cholera and assist with the development of an improved vaccine. We analyzed the V. cholerae proteins present in the stools of 32 patients with clinical cholera. The V. cholerae outer membrane porin, OmpU, was identified in all of the human stool samples, and many V. cholerae proteins were repeatedly identified in separate patient samples. The majority of V. cholerae proteins identified in human stool are involved in protein synthesis and energy metabolism. A number of proteins involved in the pathogenesis of cholera, including the A and B subunits of cholera toxin and the toxin-coregulated pilus, were identified in human stool. In a subset of stool specimens, we also assessed which in vivo expressed V. cholerae proteins were recognized uniquely by convalescent-phase as opposed to acute-phase serum from cholera patients. We identified a number of these in vivo expressed proteins as immunogenic during human infection. To our knowledge, this is the first characterization of the proteome of a pathogenic bacteria recovered from a natural host.
一种有效的霍乱弧菌疫苗尚未在霍乱疾病负担最高的发展中世界得到应用。对霍乱弧菌在人类宿主环境中表达的蛋白质进行表征,可能有助于深入了解霍乱的发病机制,并有助于开发改进的疫苗。我们分析了32例临床霍乱患者粪便中存在的霍乱弧菌蛋白质。在所有人类粪便样本中均鉴定出霍乱弧菌外膜孔蛋白OmpU,并且在不同患者样本中反复鉴定出许多霍乱弧菌蛋白质。在人类粪便中鉴定出的大多数霍乱弧菌蛋白质都参与蛋白质合成和能量代谢。在人类粪便中鉴定出了许多与霍乱发病机制有关的蛋白质,包括霍乱毒素的A和B亚基以及毒素共调节菌毛。在一部分粪便标本中,我们还评估了哪些体内表达的霍乱弧菌蛋白质被恢复期血清而非霍乱患者急性期血清独特识别。我们鉴定出许多这些体内表达的蛋白质在人类感染期间具有免疫原性。据我们所知,这是首次对从天然宿主中分离出的病原菌蛋白质组进行表征。