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首页> 外文期刊>Infection and immunity >Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity
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Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

机译：新型霍利克斯毒素变种，霍乱弧菌非O1 /非O139菌株中的ADP-核糖基化毒素及其致病性

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Cholix toxin (ChxA) is a recently discovered exotoxin in Vibrio cholerae which has been characterized as a third member of the eukaryotic elongation factor 2-specific ADP-ribosyltransferase toxins, in addition to exotoxin A of Pseudomonas aeruginosa and diphtheria toxin of Corynebacterium diphtheriae. These toxins consist of three characteristic domains for receptor binding, translocation, and catalysis. However, there is little information about the prevalence of chxA and its genetic variations and pathogenic mechanisms. In this study, we screened the chxA gene in a large number (n = 765) of V. cholerae strains and observed its presence exclusively in non-O1on-O139 strains (27.0%; 53 of 196) and not in O1 (n = 485) or O139 (n = 84). Sequencing of these 53 chxA genes generated 29 subtypes which were grouped into three clusters designated chxA I, chxA II, and chxA III. chxA I belongs to the prototype, while chxA II and chxA III are newly discovered variants. ChxA II and ChxA III had unique receptor binding and catalytic domains, respectively, in comparison to ChxA I. Recombinant ChxA I (rChxA I) and rChxA II but not rChxA III showed variable cytotoxic effects on different eukaryotic cells. Although rChxA II was more lethal to mice than rChxA I when injected intravenously, no enterotoxicity of any rChxA was observed in a rabbit ileal loop test. Hepatocytes showed coagulation necrosis in rChxA I- or rChxA II-treated mice, seemingly the major target for ChxA. The present study illustrates the potential of ChxA as an important virulence factor in non-O1on-O139 V. cholerae, which may be associated with extraintestinal infections rather than enterotoxicity.
机译：Cholix毒素（ChxA）是霍乱弧菌中最近发现的一种外毒素，除了铜绿假单胞菌的外毒素A和白喉棒状杆菌的白喉毒素外，它还被表征为真核伸长因子2特异性ADP-核糖基转移酶的第三种成员。这些毒素由受体结合​​，易位和催化作用的三个特征域组成。但是，关于 chxA 的流行及其遗传变异和致病机制的信息很少。在这项研究中，我们在大量（ n = 765）霍乱弧菌菌株中筛选了 chxA 基因，并观察到其仅在非O1 /非O139中存在菌株（27.0％; 196个中的53个），不在O1（ n = 485）或O139（ n = 84）中出现。这53个 chxA 基因的测序产生了29个亚型，这些亚型被分为三个簇，分别命名为 chxA I， chxA II和 chxA III。 chxA I属于原型，而 chxA II和 chxA III是新发现的变体。与ChxA I相比，ChxA II和ChxA III分别具有独特的受体结合和催化结构域。重组ChxA I（rChxA I）和rChxA II，但rChxA III没有对不同的真核细胞显示出可变的细胞毒性作用。尽管rChxA II对小鼠的致死性要比rChxA I静脉内注射时高，但在兔回肠loop回试验中未观察到任何rChxA的肠毒性。在rChxA I或rChxA II治疗的小鼠中，肝细胞显示出凝结坏死，这似乎是ChxA的主要靶标。本研究表明ChxA在非O1 /非O139霍乱弧菌中作为重要毒力因子的潜力，这可能与肠外感染而不是肠毒性有关。

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