Frequency and fitness consequences of bacteriophage φ6 host range mutations.
Frequency and fitness consequences of bacteriophage φ6 host range mutations.
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DOI：
10.1371/journal.pone.0113078
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dennehy JJ
中科院分区：
文献类型：
--
作者：
Ford BE;Sun B;Carpino J;Chapler ES;Ching J;Choi Y;Jhun K;Kim JD;Lallos GG;Morgenstern R;Singh S;Theja S;Dennehy JJ
病毒很容易突变并获得感染新宿主的能力，但关于允许感染任何给定新宿主的可能的宿主范围扩大突变的数量，以及这些突变对原始宿主和新宿主的适应度影响的数据很少。为了深入了解宿主范围扩展的过程，我们分离并测序了能够感染新宿主假产碱假单胞菌的 dsRNA 噬菌体 Φ6 的 69 个独立突变体。总的来说，我们在这 69 个突变体中发现了至少 17 个独特的突变组。我们检测了 17 种突变基因型中的 13 种对假产碱假单胞菌和标准实验室宿主菜豆假单胞菌的适应性。与 P.phaseolicola 相比，突变体对 P.pseudoalcaligenes 的适应性显着降低。此外，与野生型 Φ6 相比，13 个检测突变体中的 12 个显示出对 P. Phaseolicola 的适应性降低，证实了宿主范围扩张期间拮抗性多效性的普遍存在。进一步的实验表明，这些适应性差异的机制基础可能是宿主附着能力的变化。此外，使用计算蛋白质模型，我们表明宿主范围扩展突变发生在噬菌体宿主附着蛋白表面与假定的疏水锚定域相对的热点处。
Viruses readily mutate and gain the ability to infect novel hosts, but few data are available regarding the number of possible host range-expanding mutations allowing infection of any given novel host, and the fitness consequences of these mutations on original and novel hosts. To gain insight into the process of host range expansion, we isolated and sequenced 69 independent mutants of the dsRNA bacteriophage Φ6 able to infect the novel host, Pseudomonas pseudoalcaligenes. In total, we found at least 17 unique suites of mutations among these 69 mutants. We assayed fitness for 13 of 17 mutant genotypes on P. pseudoalcaligenes and the standard laboratory host, P. phaseolicola. Mutants exhibited significantly lower fitnesses on P. pseudoalcaligenes compared to P. phaseolicola. Furthermore, 12 of the 13 assayed mutants showed reduced fitness on P. phaseolicola compared to wildtype Φ6, confirming the prevalence of antagonistic pleiotropy during host range expansion. Further experiments revealed that the mechanistic basis of these fitness differences was likely variation in host attachment ability. In addition, using computational protein modeling, we show that host-range expanding mutations occurred in hotspots on the surface of the phage's host attachment protein opposite a putative hydrophobic anchoring domain.
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