Food, Nutrition and Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Institut de biologie intégrative et des systèmes (IBIS), Université Laval, Quebec City, QC G1V 0A6, Canada.
Int J Mol Sci. 2020 Mar 10;21(5):1883. doi: 10.3390/ijms21051883.
Bacteriophages have shown promise as therapeutic alternatives to antibiotics for the control of infectious bacteria, including the human pathogen However, the development of effective phage-based applications requires the elucidation of key interactions between phages and target hosts, particularly since host resistance to phage is inevitable. Little is known about the alteration of host phenotypes following the development of resistance to phage. The aim of this study is to evaluate the antibiotic susceptibility and virulence of a isolate following the development of resistance to bacteriophage SI1. We observed enhanced susceptibility to tetracycline and decreased invasion capacity in a differentiated Caco-2 intestinal cell line. Whole genome sequence analysis revealed an array of mutations, most notably, truncations in , a core gene involved in Type VI secretion and mutations in the lipopolysaccharide, thereby indicating the plausible attachment site of phage SI1. These findings shed light on understanding the underlying mechanism for phage immunity within the host. Importantly, we reveal an associated genetic cost to the bacterial host with developing resistance to phages. Taken together, these results will aid in advancing strategies to delay or eliminate the development of host resistance when designing informed phage-based antimicrobials.
噬菌体作为抗生素的治疗替代品，在控制感染性细菌方面显示出了前景，包括人类病原体 。然而，开发有效的基于噬菌体的应用需要阐明噬菌体和目标宿主之间的关键相互作用，特别是因为宿主对噬菌体的抗性是不可避免的。对于宿主表型在对噬菌体产生抗性后的改变，人们知之甚少。本研究旨在评估在对噬菌体 SI1 产生抗性后， 分离株的抗生素敏感性和毒力。我们观察到在分化的 Caco-2 肠细胞系中，对四环素的敏感性增强，侵袭能力下降。全基因组序列分析显示了一系列突变，特别是参与 VI 型分泌的核心基因 的截断和脂多糖的突变，从而表明噬菌体 SI1 的可能附着位点。这些发现揭示了宿主内噬菌体免疫的潜在机制。重要的是，我们揭示了细菌宿主在对噬菌体产生抗性时所产生的相关遗传代价。总之，这些结果将有助于在设计明智的基于噬菌体的抗菌剂时，推进延迟或消除宿主抗性发展的策略。
