School of Natural Sciences and Medicine, Ilia State University, 1 Giorgi Tsereteli exit, 0162, Tbilisi, Georgia.
Bioinformatics Core, Scientific-Research Center of Agriculture, 6 Marshal Gelovani ave, 0159, Tbilisi, Georgia.
Microb Ecol. 2022 Jul;84(1):213-226. doi: 10.1007/s00248-021-01846-0. Epub 2021 Sep 1.
Antimicrobial resistance continues to be a significant and growing threat to global public health, being driven by the emerging drug-resistant and multidrug-resistant strains of human and animal bacterial pathogens. While bacteriophages are generally known to be one of the vehicles of antibiotic resistance genes (ARGs), it remains largely unclear how these organisms contribute to the dissemination of the genetic loci encoding for antibiotic efflux pumps, especially those that confer multidrug resistance, in bacteria. In this study, the in-silico recombination analyses provided strong statistical evidence for bacteriophage-mediated intra-species recombination of ARGs, encoding mainly for the antibiotic efflux proteins from the MF superfamily, as well as from the ABC and RND families, in Salmonella enterica, Staphylococcus aureus, Staphylococcus suis, Pseudomonas aeruginosa, and Burkholderia pseudomallei. Events of bacteriophage-driven intrageneric recombination of some of these genes could be also elucidated among Bacillus thuringiensis, Bacillus cereus and Bacillus tropicus natural populations. Moreover, we could also reveal the patterns of intergeneric recombination, involving the MF superfamily transporter-encoding genetic loci, induced by a Mycobacterium smegmatis phage, in natural populations of Streptomyces harbinensis and Streptomyces chartreusis. The SplitsTree- (fit: 100; bootstrap values: 92.7-100; Phi p ≤ 0.2414), RDP4- (p ≤ 0.0361), and GARD-generated data strongly supported the above genetic recombination inferences in these in-silico analyses. Thus, based on this pilot study, it can be suggested that the above mode of bacteriophage-mediated recombination plays at least some role in the emergence and transmission of multidrug resistance across a fairly broad spectrum of bacterial species and genera including human pathogens.
抗菌药物耐药性持续对全球公共卫生构成重大且日益严重的威胁，其驱动因素是人类和动物细菌病原体中出现的耐药和多药耐药菌株。虽然噬菌体通常被认为是抗生素耐药基因 (ARGs) 的载体之一，但这些生物体如何促进编码抗生素外排泵的遗传基因座在细菌中的传播，特别是那些赋予多药耐药性的基因座，在很大程度上仍不清楚。在这项研究中，基于计算机的重组分析为噬菌体介导的沙门氏菌、金黄色葡萄球菌、猪链球菌、铜绿假单胞菌和类鼻疽伯克霍尔德菌中 ARG 的种内重组提供了强有力的统计证据，这些 ARG 主要编码 MF 超级家族的抗生素外排蛋白，以及 ABC 和 RND 家族的抗生素外排蛋白。还可以阐明一些基因在苏云金芽孢杆菌、蜡样芽孢杆菌和热带芽孢杆菌自然种群中的噬菌体驱动的种内重组事件。此外，我们还可以揭示分枝杆菌噬菌体诱导的涉及 MF 超级家族转运蛋白编码遗传基因座的种间重组模式，这种重组模式存在于自然种群的哈巴津链霉菌和桔青霉中。SplitsTree-（拟合：100；自举值：92.7-100；Phi p ≤ 0.2414）、RDP4-（p ≤ 0.0361）和 GARD 生成的数据强烈支持了这些基于计算机的分析中的上述遗传重组推断。因此，基于这项初步研究，可以认为噬菌体介导的上述重组模式至少在一定程度上导致了相当广泛的细菌物种和属（包括人类病原体）中多药耐药性的出现和传播。
