中文摘要：群体感应控制着条件致病菌铜绿假单胞菌多种重要性状，包括毒力基因及其CRISPR-cas免疫系统的表达，该免疫系统保护细菌免受噬菌体侵染。这一发现引发了一种猜测，即在噬菌体治疗过程中，合成群体感应抑制剂可用于限制CRISPR免疫的进化。本研究利用实验进化来探索群体感应抑制剂是否以及如何影响噬菌体DMS3vir感染后铜绿假单胞菌的种群和进化动态。结果发现，群体感应的化学抑制由于IV型菌毛的下调，延缓了细菌培养物的裂解，促进了CRISPR免疫的进化，从而降低了噬菌体的吸附速率。可见，抑制群体感应可能会降低而不是提高菌毛特异性噬菌体的治疗效果，这可能是噬菌体受体受到群体感应正向调节时的普遍特征。
外文摘要：Quorum sensing controls the expression of a wide range of important traits in the opportunistic pathogen Pseudomonas aeruginosa, including the expression of virulence genes and its CRISPR-cas immune system, which protects from bacteriophage (phage) infection. This finding has led to the speculation that synthetic quorum sensing inhibitors could be used to limit the evolution of CRISPR immunity during phage therapy. Here we use experimental evolution to explore if and how a quorum sensing inhibitor influences the population and evolutionary dynamics of P. aeruginosa upon phage DMS3vir infection. We find that chemical inhibition of quorum sensing decreases phage adsorption rates due to downregulation of the Type IV pilus, which causes delayed lysis of bacterial cultures and favours the evolution of CRISPR immunity. Our data therefore suggest that inhibiting quorum sensing may reduce rather than improve the therapeutic efficacy of pilus-specific phage, and this is likely a general feature when phage receptors are positively regulated by quorum sensing.
作者：Broniewski, JM；Chisnall, MAW；Hoyland-Kroghsbo, NM；Buckling, A；Westra, ER
作者单位：Univ Exeter；Univ Copenhagen
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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