Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802-4400, United States; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802-4400, United States.
Drug Resist Updat. 2016 Jul;27:30-8. doi: 10.1016/j.drup.2016.06.001. Epub 2016 Jun 6.
Bacterial chromosomes may contain up to 20% phage DNA that encodes diverse proteins ranging from those for photosynthesis to those for autoimmunity; hence, phages contribute greatly to the metabolic potential of pathogens. Active prophages carrying genes encoding virulence factors and antibiotic resistance can be excised from the host chromosome to form active phages and are transmissible among different bacterial hosts upon SOS responses. Cryptic prophages are artifacts of mutagenesis in which lysogenic phage are captured in the bacterial chromosome: they may excise but they do not form active phage particles or lyse their captors. Hence, cryptic prophages are relatively permanent reservoirs of genes, many of which benefit pathogens, in ways we are just beginning to discern. Here we explore the role of active prophage- and cryptic prophage-derived proteins in terms of (i) virulence, (ii) antibiotic resistance, and (iii) antibiotic tolerance; antibiotic tolerance occurs as a result of the non-heritable phenotype of dormancy which is a result of activation of toxins of toxin/antitoxin loci that are frequently encoded in cryptic prophages. Therefore, cryptic prophages are promising targets for drug development.
细菌染色体可能含有多达 20%的噬菌体 DNA，这些噬菌体 DNA 编码了从光合作用到自身免疫的各种蛋白质；因此，噬菌体极大地促进了病原体的代谢潜力。带有编码毒力因子和抗生素抗性基因的活性前噬菌体可以从宿主染色体上切除，形成活性噬菌体，并在 SOS 反应时在不同的细菌宿主之间传播。潜伏噬菌体是溶原性噬菌体在细菌染色体中被捕获的诱变产物：它们可以切除，但不会形成活性噬菌体颗粒或裂解它们的宿主。因此，潜伏噬菌体是基因的相对永久储存库，其中许多基因以我们才刚刚开始发现的方式使病原体受益。在这里，我们探讨了活性前噬菌体和潜伏前噬菌体衍生蛋白在以下方面的作用：（i）毒力，（ii）抗生素抗性，和（iii）抗生素耐受性；抗生素耐受性是由于休眠的非遗传性表型引起的，休眠是由于毒素/抗毒素基因座的毒素的激活引起的，这些基因座通常编码在潜伏噬菌体中。因此，潜伏噬菌体是药物开发的有前途的靶点。
