Baudry B, Fasano A, Ketley J, Kaper J B
Department of Medicine, University of Maryland School of Medicine, Baltimore.
Infect Immun. 1992 Feb;60(2):428-34. doi: 10.1128/iai.60.2.428-434.1992.
Live oral candidate cholera vaccines have previously been constructed by deletion of Vibrio cholerae sequences encoding the enzymatically active A subunit of the cholera toxin. However, volunteer studies have shown that these non-cholera toxin-producing strains still provoke mild to moderate diarrhea in some individuals. We recently reported the identification of a second toxin produced by V. cholerae which may be responsible for this residual diarrhea (A. Fasano, B. Baudry, D. W. Pumplin, S. S. Wasserman, B. D. Tall, J. M. Ketley, and J. B. Kaper, Proc. Natl. Acad. Sci. USA 88:5242-5246, 1991). This new toxigenic factor increases the permeability of rabbit ileal mucosa by affecting the structure of the intercellular tight junctions (zonula occludens). We now report the identification and cloning of the gene encoding this new toxin. This gene, named zot (for zonula occludens toxin), consists of a 1.3-kb open reading frame which could potentially encode a 44.8-kDa polypeptide. The location of the zot gene encoding the new toxin is immediately upstream of the ctx operon encoding cholera toxin.
活口服霍乱候选疫苗以前是通过删除编码霍乱毒素酶活性A亚基的霍乱弧菌序列构建的。然而，志愿者研究表明，这些不产生霍乱毒素的菌株在一些个体中仍会引发轻度至中度腹泻。我们最近报道了霍乱弧菌产生的第二种毒素的鉴定，这种毒素可能是导致这种残留腹泻的原因（A. Fasano、B. Baudry、D. W. Pumplin、S. S. Wasserman、B. D. Tall、J. M. Ketley和J. B. Kaper，《美国国家科学院院刊》88:5242 - 5246，1991年）。这种新的产毒因子通过影响细胞间紧密连接（闭锁小带）的结构增加兔回肠黏膜的通透性。我们现在报道编码这种新毒素的基因的鉴定和克隆。这个名为zot（代表闭锁小带毒素）的基因由一个1.3 kb的开放阅读框组成，该开放阅读框可能编码一个44.8 kDa的多肽。编码新毒素的zot基因位于编码霍乱毒素的ctx操纵子的紧上游。
