Program in Microbiology and Molecular Genetics (MMG), Graduate Division of Biological and Biomedical Sciences (GDBBS), Emory University School of Medicine, Atlanta, Georgia, USA.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Appl Environ Microbiol. 2019 May 16;85(11). doi: 10.1128/AEM.00209-19. Print 2019 Jun 1.
Bacteria in the genus are important targets for phage therapy due to their prevalence as pathogens and increasing antibiotic resistance. Here we review outer surface features and specific phage resistance mechanisms that define the host range, the set of strains that an individual phage can potentially infect. Phage infection goes through five distinct phases: attachment, uptake, biosynthesis, assembly, and lysis. Adsorption inhibition, encompassing outer surface teichoic acid receptor alteration, elimination, or occlusion, limits successful phage attachment and entry. Restriction-modification systems (in particular, type I and IV systems), which target phage DNA inside the cell, serve as the major barriers to biosynthesis as well as transduction and horizontal gene transfer between clonal complexes and species. Resistance to late stages of infection occurs through mechanisms such as assembly interference, in which staphylococcal pathogenicity islands siphon away superinfecting phage proteins to package their own DNA. While genes responsible for teichoic acid biosynthesis, capsule, and restriction-modification are found in most strains, a variety of other host range determinants (e.g., clustered regularly interspaced short palindromic repeats, abortive infection, and superinfection immunity) are sporadic. The fitness costs of phage resistance through teichoic acid structure alteration could make staphylococcal phage therapies promising, but host range prediction is complex because of the large number of genes involved, and the roles of many of these are unknown. In addition, little is known about the genetic determinants that contribute to host range expansion in the phages themselves. Future research must identify host range determinants, characterize resistance development during infection and treatment, and examine population-wide genetic background effects on resistance selection.
属中的细菌由于作为病原体的普遍性和抗生素耐药性的增加，成为噬菌体治疗的重要靶标。在这里，我们回顾了 噬菌体的外表面特征和特定的噬菌体抗性机制，这些机制定义了宿主范围，即单个噬菌体可以潜在感染的菌株集合。噬菌体感染经历五个不同的阶段：附着、摄取、生物合成、组装和裂解。吸附抑制，包括外表面磷壁酸受体的改变、消除或闭塞，限制了成功的噬菌体附着和进入。限制修饰系统（特别是 I 型和 IV 型系统），靶向细胞内的噬菌体 DNA，是生物合成以及克隆复合物和物种之间转导和水平基因转移的主要障碍。通过装配干扰等机制来抵抗感染的后期阶段，其中葡萄球菌致病性岛虹吸超感染噬菌体蛋白来包装自己的 DNA。虽然大多数 菌株都存在负责磷壁酸生物合成、荚膜和限制修饰的基因，但许多其他宿主范围决定因素（例如，成簇的规则间隔短回文重复序列、流产感染和超感染免疫）是分散的。通过改变磷壁酸结构来抵抗噬菌体的适应性成本可能使葡萄球菌噬菌体疗法很有前景，但由于涉及的基因数量众多，宿主范围预测很复杂，而且这些基因中的许多功能尚不清楚。此外，对于噬菌体自身宿主范围扩展的遗传决定因素知之甚少。未来的研究必须确定宿主范围决定因素，描述感染和治疗过程中抗性的发展，并检查遗传背景对抗性选择的全种群效应。
