摘要

       物种特异性噬菌体介导的抗药性基因水平遗传转移（HGT）是导致人类和动物病原菌自然种群产生抗药性菌株的重要原因，对全球公共卫生构成重大威胁。然而，多价噬菌体是否在ARGs的属间传递中起作用尚不清楚，有待进一步研究。在这项研究中，我们检测了2239个来自不同来源的噬菌体的基因组序列。然后通过PHACTS、PHAST和HostPhinder程序分析鉴定出的携带ARG的噬菌体，以确定它们的生活方式、编码细菌细胞裂解的基因、重组酶及其潜在宿主物种的光谱。我们使用SplitsTree、RDP4和SimPlot软件包进行重组试验，以确定这些噬菌体和细菌之间arg的HGT事件。在我们的分析中，一些携带精氨酸的噬菌体表现出温和和/或多价模式。SplitsTree产生的平行四边形的bootstrap值（97-100）、splits网络的fit值（97-100）、Phi P值（<10-17至3.9×10-16）、RDP4 P值（<7.8×10-03）和SimPlot结果为blaCTX-M、mel和tetM位点在种间水平上的噬菌体转导事件提供了有力的统计证据。这些事件涉及几个宿主物种，如大肠埃希菌、肠沙门氏菌、宋内志贺氏菌、肺炎链球菌和凝血杆菌。同时检测了丹毒与链球菌噬菌体间mel位点的HGT。这些结果有力地表明，某些可能具有温和性质的噬菌体诱导了blaCTX-M、mel和tetM在上述物种中的同属传播。

        The horizontal genetic transfer (HGT) of antibiotic resistance genes (ARGs) mediated by species-specific bacteriophages contributes to the emergence of antibiotic-resistant strains in natural populations of human and animal bacterial pathogens posing a significant threat to global public health. However, it is unclear and needs to be determined whether polyvalent bacteriophages play any role in the intergeneric transmission of ARGs. In this study, we examined the genome sequences of 2239 bacteriophages from different sources for the presence of ARGs. The identified ARG-carrying bacteriophages were then analyzed by PHACTS, PHAST, and HostPhinder programs to determine their lifestyles, genes coding for bacterial cell lysis, recombinases, and a spectrum of their potential host species, respectively. We employed the SplitsTree, RDP4 and SimPlot software packages in recombination tests to identify HGT events of ARGs between these bacteriophages and bacteria. In our analyses, some ARG-carrying bacteriophages exhibited temperate and/or polyvalent patterns. The bootstrap values (97-100) for the SplitsTree-generated parallelograms, fit values (97-100) for splits networks, Phi P values (< 10^-17 to 3.9 × 10^-16), RDP4 P values (≤ 7.8 × 10^-03), and the SimPlot results, provided strong statistical evidence for the phage transduction events of bla_CTX-M, mel, and tetM loci on inter-species level. These events involved several host species such as Escherichia coli, Salmonella enterica, Shigella sonnei, Streptococcus pneumoniae and Bacillus coagulans. HGT of mel loci between Erysipelothrix and Streptococcus phages were also detected. These results firmly suggest that certain bacteriophages possibly with temperate properties induce the intergeneric dissemination of bla_CTX-M, mel and tetM in the above species.

        https://link.springer.com/article/10.1007/s00284-019-01817-2