Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins.
Systematic discovery of pseudomonad genetic factors involved in sensitivity to tailocins.
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DOI：
10.1038/s41396-021-00921-1
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Arkin AP
中科院分区：
文献类型：
--
作者：
Carim S;Azadeh AL;Kazakov AE;Price MN;Walian PJ;Lui LM;Nielsen TN;Chakraborty R;Deutschbauer AM;Mutalik VK;Arkin AP
尾素是由多种细菌产生的杀菌蛋白复合物，可杀死密切相关的菌株，并可能在微生物群落结构中发挥作用。由于其高特异性，尾素已被提议作为治疗应用的精准抗菌剂。与有尾噬菌体相比，它们与尾噬菌体具有进化和形态学关系，细菌产生的尾素在产生时会杀死宿主，但产生的菌株表现出对自中毒的抵抗力。尽管脂多糖 (LPS) 已被证明可作为 tailocin 受体，但与 tailocin 敏感性相关的因素的广度以及抵抗自身中毒的机制仍不清楚。在这里，我们对四种非模型假单胞菌进行了全基因组筛选，以鉴定在密切相关的假单胞菌产生的尾素存在下适应性改变的突变体。我们的突变筛选确定了 O 抗原组成和显示对于定义对我们的 tailocins 的敏感性最重要。此外，筛选结果表明，LPS 稀释是抗性菌株对尾素更加敏感的一种机制。我们验证了许多这些新发现，并将这些对 tailocin 敏感性的观察结果扩展到 130 个基因组测序的假单胞菌。这项工作提供了对尾素与细菌相互作用的见解，为尾素在微生物组操纵和抗菌治疗中的潜在用途提供了信息。
Tailocins are bactericidal protein complexes produced by a wide variety of bacteria that kill closely related strains and may play a role in microbial community structure. Thanks to their high specificity, tailocins have been proposed as precision antibacterial agents for therapeutic applications. Compared to tailed phages, with whom they share an evolutionary and morphological relationship, bacterially produced tailocins kill their host upon production but producing strains display resistance to self-intoxication. Though lipopolysaccharide (LPS) has been shown to act as a receptor for tailocins, the breadth of factors involved in tailocin sensitivity, and the mechanisms behind resistance to self-intoxication, remain unclear. Here, we employed genome-wide screens in four non-model pseudomonads to identify mutants with altered fitness in the presence of tailocins produced by closely related pseudomonads. Our mutant screens identified O-antigen composition and display as most important in defining sensitivity to our tailocins. In addition, the screens suggest LPS thinning as a mechanism by which resistant strains can become more sensitive to tailocins. We validate many of these novel findings, and extend these observations of tailocin sensitivity to 130 genome-sequenced pseudomonads. This work offers insights into tailocin–bacteria interactions, informing the potential use of tailocins in microbiome manipulation and antibacterial therapy.
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影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.
DOI：
10.1093/bioinformatics/btq413
发表时间：
2010-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
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通讯作者：
Andersson SG
影响因子：
11
作者：
Baltrus, David A.;Clark, Meara;Hockett, Kevin L.
通讯作者：
Hockett, Kevin L.
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影响因子：
5.2
作者：
Ghequire MG;Kemland L;De Mot R
通讯作者：
De Mot R
影响因子：
4.5
作者：
Cota I;Sánchez-Romero MA;Hernández SB;Pucciarelli MG;García-Del Portillo F;Casadesús J
通讯作者：
Casadesús J