The effect of Quorum sensing inhibitors on the evolution of CRISPR-based phage immunity in Pseudomonas aeruginosa.

The effect of Quorum sensing inhibitors on the evolution of CRISPR-based phage immunity in Pseudomonas aeruginosa.
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群体感应抑制剂对铜绿假单胞菌CRISPR噬菌体免疫进化的影响。

DOI:
10.1038/s41396-021-00946-6
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发表时间:
2021-08
期刊:
The ISME journal
影响因子:
--
通讯作者:
Westra ER
Westra ER
中科院分区:
其他
文献类型:
--
作者:
Broniewski JM;Chisnall MAW;Høyland-Kroghsbo NM;Buckling A;Westra ER

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群体感应控制机会致病菌铜绿假单胞菌中广泛的重要性状的表达,包括毒力基因的表达及其CRISPR-cas免疫系统,其保护免受噬菌体(噬菌体)感染。这一发现引发了人们的猜测,即合成的群体感应抑制剂可用于限制噬菌体治疗期间CRISPR免疫的进化。在这里,我们使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DMS 3vir感染后铜绿假单胞菌的种群和进化动力学。我们发现,由于IV型菌毛的下调,群体感应的化学抑制降低了噬菌体吸附率,这导致细菌培养物的延迟裂解并有利于CRISPR免疫的进化。因此,我们的数据表明,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,这可能是一个普遍的特点时,噬菌体受体正调控的群体感应。
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.
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