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Genome-driven elucidation of phage-host interplay and impact of phage resistance evolution on bacterial fitness
The ISME Journal ( IF 11.0 ) Pub Date : 2021-08-31 , DOI: 10.1038/s41396-021-01096-5
Pawel Markwitz 1 , Cédric Lood 2, 3 , Tomasz Olszak 1 , Vera van Noort 3, 4 , Rob Lavigne 2 , Zuzanna Drulis-Kawa 1
Affiliation  

When considering the interactions between bacteriophages and their host, the issue of phage-resistance emergence is a key element in understanding the ecological impact of phages on the bacterial population. It is also an essential parameter for the implementation of phage therapy to combat antibiotic-resistant pathogens. This study investigates the phenotypic and genetic responses of five Pseudomonas aeruginosa strains (PAO1, A5803, AA43, CHA, and PAK) to the infection by seven phages with distinct evolutionary backgrounds and recognised receptors (LPS/T4P). Emerging phage-insensitivity was generally accompanied by self and cross-resistance mechanisms. Significant differences were observed between the reference PAO1 responses compared to other clinical representatives. LPS-dependent phage infections in clinical strains selected for mutations in the “global regulatory” and “other” genes, rather than in the LPS-synthesis clusters detected in PAO1 clones. Reduced fitness, as proxied by the growth rate, was correlated with large deletion (20–500 kbp) and phage carrier state. Multi-phage resistance was significantly correlated with a reduced growth rate but only in the PAO1 population. In addition, we observed that the presence of prophages decreased the lytic phage maintenance seemingly protecting the host against carrier state and occasional lytic phage propagation, thus preventing a significant reduction in bacterial growth rate.



中文翻译:

基因组驱动阐明噬菌体-宿主相互作用和噬菌体抗性进化对细菌适应度的影响

在考虑噬菌体与其宿主之间的相互作用时,噬菌体抗性出现问题是理解噬菌体对细菌种群生态影响的关键因素。它也是实施噬菌体疗法以对抗抗生素耐药性病原体的重要参数。本研究调查了五种铜绿假单胞菌的表型和遗传反应菌株(PAO1、A5803、AA43、CHA 和 PAK)对具有不同进化背景和公认受体 (LPS/T4P) 的七种噬菌体的感染。新兴的噬菌体不敏感通常伴随着自身和交叉抗性机制。与其他临床代表相比,参考 PAO1 反应之间观察到显着差异。临床菌株中的 LPS 依赖性噬菌体感染被选择用于“全局调节”和“其他”基因的突变,而不是在 PAO1 克隆中检测到的 LPS 合成簇中。以生长速率为代表的适应性降低与大缺失(20-500 kbp)和噬菌体携带状态相关。多噬菌体抗性与生长速率降低显着相关,但仅在 PAO1 群体中。此外,

更新日期:2021-08-31
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