中文摘要：由多药耐药(MDR)细菌引起的死亡率和发病率激增，促使人们对作为临床治疗剂和天然生物防治剂的噬菌体产生了新的兴趣。然而，由于共同进化的抗性机制的存在，细菌和噬菌体一直处于相互为生存而进行的进化竞赛压力下。在鼠伤寒沙门氏菌Anderson噬菌体分型方案中，与流行病学相关的确定性噬菌体类型DT104和DT104b显示出不同的噬菌体易感性。本研究旨在利用全基因组测序(WGS)研究鼠伤寒杆菌DT104和DT104b中，噬菌体耐药机制和基因组差异可能是噬菌体反应模式不同的原因。对完整的噬菌体、限制性修饰系统(RMS)、质粒和成簇的规则间隔的短回文重复序列(CRISPRs)以及与CRISPR相关的蛋白的分析显示，没有独特的遗传决定因素可以解释两种噬菌体之间易感性差异。此外，对编码潜在噬菌体受体的基因分析显示，DT104和DT104b菌株之间没有差异。然而，研究结果表明，需要对细菌细胞表面的噬菌体特异性受体进行实验评估，并使用RNA测序分析细菌转录组，以解释细菌对噬菌体敏感性的差异。采用伤寒沙门氏菌Anderson噬菌体分型方案研究细菌-噬菌体相互作用，将有助于提高对宿主-噬菌体相互作用的认识，最终推动基于噬菌体的技术发展，从而有效地控制感染。
外文摘要：The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage-host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT104 and DT104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction-modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host-phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control.
外文关键词：S；Typhimurium；DT104；DT104b；prophages；RMS；CRISPRs
作者：Mohammed, M；Orzechowska, B
作者单位：Univ Westminster
期刊名称：MICROORGANISMS
期刊影响因子：4.152
出版年份：2021
出版刊次：4
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