在当代Vibrio cholerae中,RND介导的排泄与抗菌素耐药性和高毒性相结合
Yuding Weng1, X Renee Bina1, Mia E Van Allen1
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
PLoS pathogens
|March 9, 2026
概括
当代Vibrio cholerae菌株表现出多药耐药性与高毒性相结合,挑战了以前的进化权衡理论. 维克斯B排泄将这些特征联系在一起,提供了潜在的双重治疗目标.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 进化生物学 进化生物学
背景情况:
- 由于健身成本,人们认为抗菌素耐药性和毒性是反向相关的.
- 当代Vibrio cholerae临床分离物表现出多种药物耐药性和增强的毒性.
研究的目的:
- 为了研究连接抗菌素耐药性和大流行中超病毒性的进化机制 Vibrio cholerae.
- 为了确定抗性和毒性共优化的分子基础.
主要方法:
- 对当代 (第3波,2017-2019年) 和早期大流行的Vibrio cholerae分离物进行比较分析.
- 对67个O1埃尔托尔基因组 (1960-2019) 的遗传学分析.
- 在小鼠模型中对VexB排泄进行基因操纵,并评估其对抗性和殖民性的影响.
主要成果:
- 当代隔离物显示出广泛的抗微生物耐药性,并在婴儿小鼠中增强了殖民.
- 韦克斯B RND 排泄被确定为多药耐药性和高毒性中介.
- 维克斯B无活化减少了抵抗和殖民,而高表达增加了抵抗.
- 维克斯B介导的高毒性涉及独立于霍乱毒素和毒素对调节的毒素的途径.
结论:
- 维克斯B作为抗菌素耐药性和大流行中超病毒性之间的分子链接 Vibrio cholerae.
- 像VexB这样的Efflux代表了对抗抗性和毒性菌株的双重功能治疗目标.
- 自然选择有利于在最近的Vibrio cholerae进化中对抗性和毒性进行共同优化.
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