中文摘要：在考虑噬菌体与其宿主之间的相互作用时，噬菌体耐药性的出现是理解噬菌体对细菌种群生态影响的关键因素；它也是实施噬菌体治疗，对抗抗生素耐药性病原体的重要参数。本研究调查了五株铜绿假单胞菌（PAO1、A5803、AA43、CHA和PAK）对七种不同进化背景和受体（LPS/T4P）的噬菌体感染的表型和遗传反应。发现噬菌体不敏感的出现通常伴随着自身和交叉耐药机制；与其他临床代表相比，参考PAO1反应之间存在显著差异；临床菌株中LPS依赖的噬菌体感染选择的突变是“全局调控”和“其他”基因，而不是在PAO1克隆中检测到的LPS-合成簇；以生长速率表示的适应度降低与大片段缺失（20-500kbp）和噬菌体载体状态相关；多噬菌体耐药性与生长率速降低显著相关，但仅存在于PAO1群体中。此外，原噬菌体的存在减少了裂解噬菌体的维持，保护了宿主免受载体状态和偶尔的裂解噬菌体繁殖的影响，从而防止了细菌生长速率的显著降低。
外文摘要：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.
外文关键词：PSEUDOMONAS-AERUGINOSA；IMMUNE-SYSTEM；BACTERIOPHAGE；DEFENSE；ADAPTATION
作者：Markwitz, P；Lood, C；Olszak, T；van Noort, V；Lavigne, R；Drulis-Kawa, Z
作者单位：Univ Wroclaw；Katholieke Univ Leuven；Leiden Univ
期刊名称：ISME JOURNAL
期刊影响因子：9.18
出版年份：2021
出版刊次：
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