Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins.
Successful small intestine colonization of adult mice by Vibrio cholerae requires ketamine anesthesia and accessory toxins.
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DOI：
10.1371/journal.pone.0007352
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发表时间：
2009-10-08
期刊：
影响因子：
3.7
通讯作者：
Satchell KJ
中科院分区：
文献类型：
--
作者：
Olivier V;Queen J;Satchell KJ
霍乱弧菌定植于成年C57 BL/6小鼠的小肠。在这项研究中，物理和遗传参数，促进这种殖民化进行了调查。成功的殖民地被发现依赖于麻醉氯胺酮，甲苯噻嗪和中和胃酸碳酸氢钠，但不是链霉素治疗。O 1、O 139和非O 1/非O 139品系在多种常见小鼠品系中定殖。评估溶血素、多功能、自加工RTX毒素（MARTX）和血凝素/蛋白酶基因中突变体的所有组合，发现溶血素和MARTX各自足以在低剂量感染后定植。总的来说，这项研究表明，胃内接种后，霍乱弧菌遇到感染障碍，包括酸性环境和立即免疫反应，这是由碳酸氢钠和氯胺酮-甲苯噻嗪的抗炎作用规避。在小肠中初始粘附后，细菌受到额外的清除机制的影响，这些机制被溶血素或MARTX的独立毒性作用所逃避。一旦建立定植，这表明，在人类中，这些现在持续存在的细菌开始合成导致霍乱疾病的主要毒力因子。这种肠道霍乱弧菌感染的成年小鼠模型，目前已得到充分表征和充分优化，应作为研究发病机制和测试疫苗效力的有价值的工具。
Vibrio cholerae colonizes the small intestine of adult C57BL/6 mice. In this study, the physical and genetic parameters that facilitate this colonization were investigated. Successful colonization was found to depend upon anesthesia with ketamine-xylazine and neutralization of stomach acid with sodium bicarbonate, but not streptomycin treatment. A variety of common mouse strains were colonized by O1, O139, and non-O1/non-O139 strains. All combinations of mutants in the genes for hemolysin, the multifunctional, autoprocessing RTX toxin (MARTX), and hemagglutinin/protease were assessed, and it was found that hemolysin and MARTX are each sufficient for colonization after a low dose infection. Overall, this study suggests that, after intragastric inoculation, V. cholerae encounters barriers to infection including an acidic environment and an immediate immune response that is circumvented by sodium bicarbonate and the anti-inflammatory effects of ketamine-xylazine. After initial adherence in the small intestine, the bacteria are subjected to additional clearance mechanisms that are evaded by the independent toxic action of hemolysin or MARTX. Once colonization is established, it is suggested that, in humans, these now persisting bacteria initiate synthesis of the major virulence factors to cause cholera disease. This adult mouse model of intestinal V. cholerae infection, now well-characterized and fully optimized, should serve as a valuable tool for studies of pathogenesis and testing vaccine efficacy.
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DOI：
10.1038/icb.1975.14
发表时间：
1975-01-01
期刊：
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE
影响因子：
--
作者：
KNOP, J;ROWLEY, D
通讯作者：
ROWLEY, D
影响因子：
3.1
作者：
HANNE, LF;FINKELSTEIN, RA
通讯作者：
FINKELSTEIN, RA
影响因子：
11.4
作者：
Fullner, KJ;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
15.3
作者：
Fullner, KJ;Boucher, JC;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3.1
作者：
Helmer, KS;Cui, Y;Mercer, DW
通讯作者：
Mercer, DW