肠道环境增强了菌体适应Salmonella Typhimurium的表型耐药性的反应
Nicolas Wenner1, Anouk Bertola1, Louise Larsson1,2
1Biozentrum, University of Basel, Basel CH-4056, Switzerland.
概括
细菌O-抗原相变允许暂时的菌体共存. 然而,肠道状况加速了菌体的进化,使菌体能够克服细菌的抵抗力,并导致耐药细菌的选择.
科学领域:
- 微生物学 微生物学
- 进化生物学 进化生物学
- 遗传学 遗传学 是一个
背景情况:
- 细菌群体表现出异质基因表达,允许与毒性菌体共存.
- 通过Salmonella Typhimurium (S.Tm) 的O-抗原相变的表型耐药性赋予了对T5类菌体37 (Φ37) 的耐药性.
- 菌体进化能力和健康成本挑战了菌体与细菌共存的稳定性,影响了菌体治疗的成功.
研究的目的:
- 为了研究不同条件下的菌体-细菌共存的进化稳定性.
- 确定O-抗原相变在介导耐药性和共存中的作用.
- 了解肠道状况如何影响菌体进化和细菌耐药性.
主要方法:
- 在液体培养中对菌细菌动态的比较分析与小鼠肠道模型.
- 在模仿肠道环境的条件下,体外对菌体的实验进化.
- 细菌耐药机制的基因型和表型特征.
主要成果:
- 阶段变化促进了长时间的菌体-Salmonella Typhimurium在液体介质中的共存.
- 在小鼠肠道中,相位变化只会延迟遗传耐药性STM突变的出现.
- 进化的菌体出现了,可以感染敏感和耐药的S.Tm变体,选择耐药突变物.
- 在粘性介质中的体外进化模仿了在肠道中观察到的快速菌体进化.
结论:
- 肠道状况通过增强扩大宿主范围的突变来加速菌体进化.
- 肠道中的菌体进化否定了O-抗原相变的保护作用.
- 这种动态对预测共同进化轨迹和菌体治疗的有效性有重大影响.
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