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首页> 外文期刊>Applied Microbiology >Bacteriophage Resistance Mechanisms in the Fish Pathogen Flavobacterium psychrophilum: Linking Genomic Mutations to Changes in Bacterial Virulence Factors
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Bacteriophage Resistance Mechanisms in the Fish Pathogen Flavobacterium psychrophilum: Linking Genomic Mutations to Changes in Bacterial Virulence Factors

机译：鱼病原体黄杆菌黄杆菌的噬菌体抗性机制：基因突变与细菌毒力因子的变化联系起来。

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Flavobacterium psychrophilum is an important fish pathogen in salmonid aquaculture worldwide. Due to increased antibiotic resistance, pathogen control using bacteriophages has been explored as a possible alternative treatment. However, the effective use of bacteriophages in pathogen control requires overcoming the selection for phage resistance in the bacterial populations. Here, we analyzed resistance mechanisms in F. psychrophilum after phage exposure using whole-genome sequencing of the ancestral phage-sensitive strain 950106-1/1 and six phage-resistant isolates. The phage-resistant strains had all obtained unique insertions and/or deletions and point mutations distributed among intergenic and genic regions. Mutations in genes related to cell surface properties, gliding motility, and biosynthesis of lipopolysaccharides and cell wall were found. The observed links between phage resistance and the genetic modifications were supported by direct measurements of bacteriophage adsorption rates, biofilm formation, and secretion of extracellular enzymes, which were all impaired in the resistant strains, probably due to superficial structural changes. The clustered regularly interspaced short palindromic repeat (CRISPR) region was unaffected in the resistant isolates and thus did not play a role as a resistance mechanism for F. psychrophilum under the current conditions. All together, the results suggest that resistance in F. psychrophilum was driven by spontaneous mutations, which were associated with a number of derived effects on the physiological properties of the pathogen, including reduced virulence under in vitro conditions. Consequently, phage-driven physiological changes associated with resistance may have implications for the impact of the pathogen in aquaculture, and these effects of phage resistance on host properties are therefore important for the ongoing exploration of phage-based control of F. psychrophilum .
机译：精神黄杆菌是全世界鲑鱼养殖中的重要鱼类病原体。由于增加的抗生素抗性，已经探索了使用噬菌体控制病原体作为可能的替代治疗方法。然而，噬菌体在病原体控制中的有效利用需要克服细菌种群中噬菌体抗性的选择。在这里，我们使用祖传噬菌体敏感菌株950106-1 / 1的全基因组测序和六个噬菌体抗性分离株，分析了噬菌体暴露后嗜热镰刀菌的抗性机制。噬菌体抗性菌株均获得了独特的插入和/或缺失，并且点突变分布在基因间和基因区域之间。发现与细胞表面特性，滑行运动以及脂多糖和细胞壁的生物合成有关的基因突变。通过直接测量噬菌体的吸附速率，生物膜形成和细胞外酶的分泌，可以支持在噬菌体抗性和基因修饰之间观察到的联系，这可能是由于表面结构的改变而在抗性菌株中受损。聚簇的规则间隔的短回文重复序列（CRISPR）区域在抗性分离株中不受影响，因此在当前条件下不作为对嗜热镰刀菌的抗性机制。总之，这些结果表明，自发突变导致了嗜热镰刀菌的抗药性，这与对病原体生理特性的许多衍生作用有关，包括在体外条件下降低的毒力。因此，与抗性相关的噬菌体驱动的生理变化可能对水产养殖中病原体的影响有影响，因此，噬菌体抗性对宿主特性的这些影响对于正在进行的基于噬菌体的嗜冷镰孢菌控制的探索很重要。

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