School of Life Sciences, University of Warwickgrid.7372.1, Coventry, United Kingdom.
Milner Centre for Evolution, Department of Biology & Biochemistry, University of Bathgrid.7340.0, Bath, United Kingdom.
Microbiol Spectr. 2022 Jun 29;10(3):e0211221. doi: 10.1128/spectrum.02112-21. Epub 2022 Apr 25.
Reviewing the genetics underlying the arms race between bacteria and bacteriophages can offer an interesting insight into the development of bacterial resistance and phage co-evolution. This study shows how the natural development of resistances to the K1F bacteriophage, a phage which targets the K1 capsule of pathogenic Escherichia coli, can come about through insertion sequences (IS). Of the K1F resistant mutants isolated, two were of particular interest. The first of these showed full resistance to K1F and was found to have disruptions to , the product of which is involved in polysialic acid translocation. The second, after showing an initial susceptibility to K1F which then developed to full resistance, had disruptions to , a gene involved in one of the early steps of polysialic acid biosynthesis. Both of these mutations came with a fitness cost and produced considerable phenotypic differences in the completeness and location of the K1 capsule when compared with the wild type. Sequential treatment of these two K1F resistant mutants with T7 resulted in the production of a variety of isolates, many of which showed a renewed susceptibility to K1F, indicating that these insertion sequence mutations are reversible, as well as one isolate that developed resistance to both phages. Bacteriophages have many potential uses in industry and the clinical environment as an antibacterial control measure. One of their uses, phage therapy, is an appealing alternative to antibiotics due to their high specificity. However, as with the rise in antimicrobial resistance (AMR), it is critical to improve our understanding of how resistance develops against these viral agents. In the same way as bacteria will evolve and mutate antibiotic receptors so they can no longer be recognized, resistance to bacteriophages can come about via mutations to phage receptors, preventing phage binding and infection. We have shown that Escherichia coli will become resistant to the K1F bacteriophage via insertion element reshufflings causing null mutations to elements of the polysialic acid biosynthetic cluster. Exposure to the T7 bacteriophage then resulted in further changes in the position of these IS elements, further altering their resistance and sensitivity profiles.
审查细菌和噬菌体之间军备竞赛的遗传基础，可以为细菌耐药性和噬菌体共同进化的发展提供有趣的见解。这项研究表明，针对致病性大肠杆菌 K1 荚膜的 K1F 噬菌体的自然耐药性是如何通过插入序列 (IS) 产生的。在所分离的 K1F 抗性突变体中，有两个特别有趣。其中第一个对 K1F 表现出完全抗性，并且发现其产物 被破坏，该产物参与多涎酸的转运。第二个在最初对 K1F 表现出敏感性，然后发展为完全抗性，其产物 被破坏，该基因参与多涎酸生物合成的早期步骤之一。这两种突变都伴随着适应度的代价，并与野生型相比，在 K1 荚膜的完全性和位置上产生了相当大的表型差异。用 T7 对这两种 K1F 抗性突变体进行连续处理，产生了多种分离株，其中许多对 K1F 重新表现出敏感性，这表明这些插入序列突变是可逆的，并且有一种分离株对两种噬菌体都产生了耐药性。噬菌体在工业和临床环境中作为一种抗菌控制措施具有许多潜在用途。噬菌体治疗是抗生素的一种有吸引力的替代方法，因为它们具有很高的特异性。然而，随着抗菌药物耐药性 (AMR) 的增加，了解耐药性如何针对这些病毒制剂发展至关重要。就像细菌会进化和突变抗生素受体，使其不再被识别一样，噬菌体的耐药性也可以通过噬菌体受体的突变来产生，从而阻止噬菌体的结合和感染。我们已经表明，大肠杆菌会通过插入元件的重新排列而对 K1F 噬菌体产生抗性，从而导致多涎酸生物合成簇的元件发生无效突变。然后暴露于 T7 噬菌体会导致这些 IS 元件的位置发生进一步变化，进一步改变它们的耐药性和敏感性谱。
