Parsot C, Taxman E, Mekalanos J J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1641-5. doi: 10.1073/pnas.88.5.1641.
The genes encoding three lipoproteins of Vibrio cholerae were identified by a combination of DNA sequence analysis and [3H]palmitate labeling of hybrid proteins encoded by TnphoA gene fusions. The expression of these three lipoproteins, TagA, AcfD, and TcpC, was controlled by ToxR, the cholera toxin transcriptional activator. The involvement of other bacterial lipoproteins in conferring resistance to the bactericidal effects of complement prompted us to examine this possibility in V. cholerae. Remarkably, mutations in toxR and tcp genes (including tcpC), involved in the biogenesis of the toxin coregulated pili, rendered V. cholerae about 10(4)-10(6) times more sensitive to the vibriocidal activity of antibody and complement. Since V. cholerae is a noninvasive organism and toxR and tcp mutants are highly defective in intestinal colonization in animals and humans, these results raise the possibility that resistance to a gut-associated, "complement-like" bactericidal activity may be a major virulence determinant of V. cholerae and other enterobacterial species.
通过DNA序列分析以及对TnphoA基因融合所编码的杂交蛋白进行[3H]棕榈酸酯标记相结合的方法，鉴定出了霍乱弧菌三种脂蛋白的编码基因。这三种脂蛋白TagA、AcfD和TcpC的表达受霍乱毒素转录激活因子ToxR的调控。其他细菌脂蛋白参与赋予对补体杀菌作用的抗性，这促使我们在霍乱弧菌中研究这种可能性。值得注意的是，参与毒素共调节菌毛生物合成的toxR和tcp基因（包括tcpC）发生突变，使霍乱弧菌对抗体和补体的杀弧菌活性敏感约10^4 - 10^6倍。由于霍乱弧菌是一种非侵袭性生物体，且toxR和tcp突变体在动物和人类肠道定殖方面存在高度缺陷，这些结果提示，对肠道相关的“补体样”杀菌活性的抗性可能是霍乱弧菌和其他肠杆菌科细菌的主要毒力决定因素。
