Thung Tze Y, Hall Alex, Jati Afif P, White Murray E, Bamert Rebecca S, Tan Kher Shing, Press Cara, Taiaroa George, Short Francesca L, Dunstan Rhys A, Lithgow Trevor
Center to Impact AMR, Monash University, Clayton, Australia.
Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Australia.
mBio. 2024 Dec 11;15(12):e0256424. doi: 10.1128/mbio.02564-24. Epub 2024 Oct 30.
In a survey of a waterway on Wurundjeri land, two sub-populations of the bacteriophage Merri-merri-uth nyilam marra-natj (phage MMNM) were isolated on a permissive host, B5055 of capsule-type K2, but were distinguished by minor phenotypic differences. The variant phage MMNM(Ala) showed an inhibited activity against AJ174-2, and this was used as a basis to select for further variation through experimental evolution. Over the course of an evolution experiment, 20 phages that evolved distinct phenotypes in terms of the morphologies of plaques formed when they infected host were subject to whole-genome sequencing. The evolved phages had mutations in a small set of proteins that contribute to the baseplate portion of the phage virion. Phages MMNM and MMNM(Ala) are minimalist phages, with baseplates formed from only five predicted subunits, akin to other minimalist phages Pam3 and XM1. The homology between all three minimalist phages provided a structural framework to interpret the two classes of mutations derived through evolution in the presence of the semi-permissive host: those that affect the interfacial surfaces between baseplate subunits, and those in a base-plate associated tail-fiber. This study evidences that multiple small mutations can be fixed into a sub-population of phage to provide a basis for phenotypic variation that we suggest could ultimately provide for a shift of virus properties, as an alternative evolutionary scenario to the major genetic events that result in more well-studied evolutionary mechanism of phage mosaicism.
Bacteriophages (phages) are viruses that prey on bacteria. This study sampled natural phage populations to test the hypothesis that untapped genetic variation within a population can be the basis for the selection of phages to diversify their host-range. Sampling of a freshwater site revealed two populations of the phage Merri-merri-uth nyilam marra-natj (phage MMNM), differing by a variant residue (Val134Ala) in the baseplate protein MMNM_26. This sequence variation modulated bacterial killing in plaques, and further evolution of the phages on a semi-permissive bacterial host led to a new generation of phages with more diverse phenotypes in killing the bacterium .
在对乌鲁恩杰里土地上一条水道的调查中，噬菌体梅里 - 梅里 - 乌思·尼拉姆·马拉 - 纳季（噬菌体MMNM）的两个亚群在允许性宿主——K2型荚膜的B5055上被分离出来，但通过微小的表型差异得以区分。变异噬菌体MMNM(Ala)对AJ174 - 2表现出抑制活性，并以此为基础通过实验进化来选择进一步的变异。在进化实验过程中，对20个在感染宿主时形成的噬菌斑形态方面进化出不同表型的噬菌体进行了全基因组测序。进化后的噬菌体在一小部分有助于噬菌体病毒粒子基板部分的蛋白质中发生了突变。噬菌体MMNM和MMNM(Ala)是极简主义噬菌体，其基板仅由五个预测的亚基组成，类似于其他极简主义噬菌体Pam3和XM1。这三种极简主义噬菌体之间的同源性提供了一个结构框架，以解释在半允许性宿主存在的情况下通过进化产生的两类突变：那些影响基板亚基之间界面表面的突变，以及那些在与基板相关的尾纤维中的突变。这项研究证明，多个小突变可以在噬菌体亚群中固定下来，为表型变异提供基础，我们认为这最终可能导致病毒特性的转变，作为一种替代进化情景，不同于导致噬菌体镶嵌现象这一研究更深入的进化机制的主要遗传事件。
噬菌体是以细菌为食的病毒。本研究对天然噬菌体群体进行采样，以检验一个假设，即群体内未开发的遗传变异可以成为选择噬菌体以使其宿主范围多样化的基础。对一个淡水地点的采样揭示了噬菌体梅里 - 梅里 - 乌思·尼拉姆·马拉 - 纳季（噬菌体MMNM）的两个群体，它们在基板蛋白MMNM_26中的一个变异残基（Val134Ala）上存在差异。这种序列变异调节了噬菌斑中的细菌杀伤作用，并且噬菌体在半允许性细菌宿主上的进一步进化导致了新一代在杀死细菌方面具有更多样化表型的噬菌体。
