Department of Civil and Environmental Engineering, Rice University, Houston, Texas, USA.
Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Appl Environ Microbiol. 2024 Oct 23;90(10):e0095124. doi: 10.1128/aem.00951-24. Epub 2024 Sep 9.
Bacteriophages offer an opportunity for chemical-free, precise control of problematic bacteria, but this approach can be limited when lytic phages are difficult to obtain for the target host. In such cases, phage-based targeting of cooperating or cross-feeding bacteria (e.g., ) can be an effective approach to control the problematic bacteria (e.g., ). Using a dual-species biofilm system, phage predation of (10 PFU·mL) decreased the abundance of pathogenic by >99% compared with no-treatment controls, while also inhibiting the production of cytotoxic metabolic end products (butyric and propionic acids). Phage treatment upregulated genes associated with interspecies co-adhesion (5- to 8-fold) and quorum sensing (10-fold) in residual , which is conducive to increased potential to bind to . Counterintuitively, lower-titer phage applications (10 PFU·mL) increased the production of extracellular polymeric substance (EPS) by 22% and biofilm biomass by 50%. This overproduction of EPS may contribute to the phenomenon where the biofilm separated into two distinct species layers, as observed by confocal laser scanning microscopy. Although more complex mixed-culture systems should be considered to delineate the merits and limitations of this novel biocontrol approach (which would likely require the use of phage cocktails), our results offer proof of concept that indirect phage-based targeting can expand the applicability of phage-based control of pathogenic bacteria for public health protection.
Lytic phages are valuable agents for targeted elimination of bacteria in diverse applications. Nevertheless, lytic phages are difficult to isolate for some target pathogens. We offer proof of concept that this limitation may be overcome via indirect phage targeting, which involves knocking out species that interact closely with and benefit the primary problematic target bacteria. Our target () only forms a periodontal pathogenic biofilm if the pioneer colonizer () offers its surface for to attach. Phage predation of the co-adhesive significantly reduced abundance of the target pathogen by >99%, decreased the total biofilm biomass by >44%, and suppressed its production of cytotoxic metabolic byproducts. Thus, this research extends the scope of phage-based biocontrol for public health protection.
噬菌体为控制有问题的细菌提供了一种无化学物质、精确的方法，但当目标宿主难以获得裂解噬菌体时，这种方法可能会受到限制。在这种情况下，基于噬菌体的合作或交叉喂养细菌的靶向（例如，）可以是控制有问题的细菌（例如，）的有效方法。使用双物种生物膜系统，噬菌体捕食（10 PFU·mL）使致病性（>99%与无处理对照相比）的丰度降低，同时还抑制了细胞毒性代谢副产物（丁酸和丙酸）的产生。噬菌体处理上调了与种间共附着（5-8 倍）和群体感应（10 倍）相关的基因，这有利于增加与的结合潜力。反直觉的是，较低滴度的噬菌体应用（10 PFU·mL）使细胞外聚合物（EPS）的产量增加了 22%，生物膜生物量增加了 50%。这种 EPS 的过度产生可能导致生物膜分成两个不同的物种层，如共聚焦激光扫描显微镜观察到的那样。尽管应该考虑更复杂的混合培养系统来描绘这种新型生物控制方法的优点和局限性（这可能需要使用噬菌体鸡尾酒），但我们的结果提供了概念验证，表明间接基于噬菌体的靶向可以扩大噬菌体控制致病性细菌用于公共卫生保护的适用性。
裂解噬菌体是针对多种应用中细菌进行靶向消除的有价值的试剂。然而，对于一些目标病原体来说，裂解噬菌体很难分离。我们提供了概念验证，即这种限制可以通过间接噬菌体靶向来克服，这种方法涉及敲除与主要有问题的目标细菌密切相互作用并受益于其的物种。我们的目标（）只有在先驱定植体（）为其提供表面以供附着时才会形成牙周病病原体生物膜。噬菌体捕食共生的（）使目标病原体的丰度降低了>99%，生物膜总生物量降低了>44%，并抑制了其细胞毒性代谢副产物的产生。因此，这项研究扩展了噬菌体生物控制在公共卫生保护方面的应用范围。
