中文摘要：细菌的蛋白质和糖缀合物表面结构有助于形成生物膜，并为宿主防御机制（如补体系统和吞噬作用）提供屏障。这些分子的丢失或改变会引起噬菌体耐药性产生，也会导致毒性细菌的减少。本研究评估了噬菌体处理的生物膜中出现的铜绿假单胞菌PAO1耐噬菌体克隆的生物学和表型变化，描述了这些克隆的噬菌体分型模式、抗生素耐药性、生物膜形成、致病性以及与先天免疫系统的相互作用；还解决了另一个重要问题：尽管存在噬菌体治疗选择压力，但作为生物膜种群的自然适应，是否也会偶然产生噬菌体耐药突变体。研究发现，针对特定受体的不同噬菌体的应用选择了相似的噬菌体耐药模式，但导致种群异质性显著增加，与未经处理的PAO1固着型相比，产生了十几种噬菌体分型模式；证实了一种假说，即“耐噬菌体细菌更易受到抗生素和宿主免疫系统清除机制的影响”。可见，这些发现支持噬菌体在治疗中的应用，当然噬菌体治疗选择毒性较低的细菌群体这一总体说法还有待用更多的临床菌株进一步验证。
外文摘要：Bacterial surface structures of a proteinic nature and glycoconjugates contribute to biofilm formation and provide shields to host defense mechanisms (e.g., the complement system and phagocytosis). A loss or alteration of these molecules, leading to phage resistance, could result in fewer virulent bacteria. In this study, we evaluate the biology and phenotype changes in Pseudomonas aeruginosa PAO1 phage-resistant clones, which emerge in phage-treated biofilms. We characterize these clones for phage-typing patterns, antibiotic resistance, biofilm formation, pathogenicity, and interactions with the innate immune system. Another important question that we address is whether phage-resistant mutants are also generated incidentally, despite the phage treatment-selective pressure, as the natural adaptation of the living biofilm population. It is found that the application of different phages targeting a particular receptor selects similar phage resistance patterns. Nevertheless, this results in a dramatic increase in the population heterogeneity, giving over a dozen phage-typing patterns, compared to one of the untreated PAO1 sessile forms. We also confirm the hypothesis that "phage-resistant bacteria are more susceptible to antibiotics and host-clearance mechanisms by the immune system". These findings support phage application in therapy, although the overall statement that phage treatment selects the less virulent bacterial population should be further verified using a bigger collection of clinical strains.
外文关键词：Pseudomonas aeruginosa；biofilm；phage-resistant mutants；virulence；heterogeneity
作者：Markwitz, P；Olszak, T；Gula, G；Kowalska, M；Arabski, M；Drulis-Kawa, Z
作者单位：Univ Wroclaw；Jan Kochanowski Univ Humanities & Sci
期刊名称：VIRUSES-BASEL
期刊影响因子：3.816
出版年份：2021
出版刊次：7
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