Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage

Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage
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DOI:
10.1073/pnas.96.3.1071
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发表时间:
1999-02-02
影响因子:
11.1
通讯作者:
Mekalanos, JJ
Mekalanos, JJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lin, W;Fullner, KJ;Mekalanos, JJ

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我们鉴定并表征了F1 Tor霍乱弧菌中编码体外对HEp-2细胞的细胞毒性活性的基因簇。该基因簇包含四个基因,并且与霍乱弧菌基因组中的霍乱毒素(CTX)元件物理连接。我们通过插入突变证明了这个基因簇是细胞毒活性所必需的,毒素RtxA类似于RTX的成员,与其他RTX毒素一样,其活性取决于激活剂RtxC和相关的ABC转运系统RtxB和RtxD。在经典生物型的霍乱弧菌菌株中,基因簇内的缺失除去rtxC并消除细胞毒性活性。其他菌株,包括目前霍乱大流行的菌株,含有功能性基因簇并显示细胞毒性活性。因此,F1 Tor O 1和O 139菌株中的RTX基因簇可能对它们的出现有显著贡献。此外,霍乱弧菌的RTX毒素可能与某些减毒活霍乱疫苗显示的残留不良特性有关。
We identify and characterize a gene cluster in Fl Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro, This gene cluster contains four genes and is physically linked to the cholera toxin (CTX) element in the V. cholerae genome. We demonstrate by using insertional mutagenesis that this gene cluster is required for the cytotoxic activity, The toxin, RtxA, resembles members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich repeated motif, Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, RtxB and RtxD, In V. cholerae strains of the classical biotype, a deletion within the gene cluster removes rtxC and eliminates cytotoxic activity. Other strains, including those of the current cholera pandemic, contain a functional gene cluster and display cytotoxic activity. Thus, the RTX gene cluster in Fl Tor O1 and O139 strains might have contributed significantly to their emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated cholera vaccines.