Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Viruses. 2024 May 8;16(5):743. doi: 10.3390/v16050743.
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the virulence of priority 1 nosocomial pathogenic bacterium, . By subjecting phage-resistant variant Ev5-WHG of WHG40004 to several virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in .
噬菌体对其细菌宿主施加强大的选择压力,以促使其进化出抗性。与此同时,噬菌体抗性后对细菌的适应成本可能会改变其毒力,从而可能影响噬菌体治疗的治疗效果。在这项研究中,我们着手评估噬菌体抗性对优先级 1 医院获得性致病细菌 的毒力的代价。通过使 WHG40004 的噬菌体抗性变体 Ev5-WHG 经历几种毒力特征,我们发现其对噬菌体的抗性与宿主微环境中适应性降低有关。此外,该突变体对哺乳动物细胞的黏附和侵袭能力受损,对巨噬细胞吞噬作用的敏感性增加。此外,突变体的全基因组测序表明,存在多个可能在噬菌体抗性和改变的毒力中起作用的突变。总的来说,这项研究表明,噬菌体的抗性可以显著改变 与毒力相关的表型。