School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Sci Rep. 2019 Mar 12;9(1):4293. doi: 10.1038/s41598-019-40223-3.
In assessing the potential of predatory bacteria, such as Bdellovibrio bacteriovorus, to become live therapeutic agents against bacterial infections, it is crucial to understand and quantify Bdellovibrio host cell interactions at a molecular level. Here, we quantify the interactions of live B. bacteriovorus with human phagocytic cells, determining the uptake mechanisms, persistence, associated cytokine responses and intracellular trafficking of the non-growing B. bacteriovorus in PMA-differentiated U937 cells. B. bacteriovorus are engulfed by U937 cells and persist for 24 h without affecting host cell viability and can be observed microscopically and recovered and cultured post-uptake. The uptake of predators is passive and depends on the dynamics of the host cell cytoskeleton; the engulfed predators are eventually trafficked through the phagolysosomal pathway of degradation. We have also studied the prevalence of B. bacteriovorus specific antibodies in the general human population. Together, these results quantify a period of viable persistence and the ultimate fate of B. bacteriovorus inside phagocytic cells. They provide new knowledge on predator availability inside hosts, plus potential longevity and therefore potential efficacy as a treatment in humans and open up future fields of work testing if predators can prey on host-engulfed pathogenic bacteria.
在评估掠夺性细菌（如 Bdellovibrio bacteriovorus）成为治疗细菌感染的活体治疗剂的潜力时，了解和量化 Bdellovibrio 与宿主细胞的相互作用至关重要。在分子水平上。在这里，我们量化了活的 B. bacteriovorus 与人类吞噬细胞的相互作用，确定了摄取机制、持久性、与非生长的 B. bacteriovorus 相关的细胞因子反应以及 PMA 分化的 U937 细胞中的细胞内转运。B. bacteriovorus 被 U937 细胞吞噬，并在不影响宿主细胞活力的情况下持续 24 小时，并且可以在摄取后进行微观观察和回收培养。捕食者的摄取是被动的，取决于宿主细胞细胞骨架的动态；吞噬的捕食者最终通过溶酶体降解途径进行运输。我们还研究了 B. bacteriovorus 特异性抗体在普通人群中的流行情况。总之，这些结果量化了吞噬细胞内 B. bacteriovorus 存活的持续时间和最终命运。它们提供了有关宿主内捕食者可用性的新知识，加上潜在的寿命，因此作为人类治疗的潜在疗效，并开辟了未来的工作领域，以测试捕食者是否可以捕食宿主吞噬的致病性细菌。
