Atto Brianna, Kunde Dale, Gell David A, Tristram Stephen
School of Health Sciences, University of Tasmania, Newnham Drive, Launceston, TAS 7248, Australia.
School of Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia.
Pathogens. 2021 Jan 1;10(1):29. doi: 10.3390/pathogens10010029.
Nontypeable (NTHi) is a significant respiratory tract pathogen responsible for infections that collectively pose a substantial health and socioeconomic burden. The clinical course of these infections is largely dictated by NTHi interactions with host respiratory epithelia, and thus, approaches that disrupt colonisation and invasion may have significant therapeutic potential. Survival, successful host-cell interactions, and pathogenesis are reliant on NTHi's ability to sequester host-derived haem. Previously, we demonstrated the therapeutic potential of exploiting this haem-dependence using a closely related competitor bacterium, (Hh). Hh strains capable of producing the novel haem-binding protein haemophilin (Hpl) possessed potent inhibitory activity by restricting NTHi access to haem in a broth co-culture environment. Here, we extend this work to cell culture models that more closely represent the human respiratory epithelium and show that Hh strains with high levels of expression protect epithelial cell line monolayers against adhesion and invasion by NTHi. Inhibitory activity was dependent on the level of Hpl production, which was stimulated by NTHi challenge and nasopharyngeal cell exposure. Provided these protective benefits translate to in vivo applications, Hpl-producing Hh may have probiotic utility against NTHi infections by inhibiting requisite nasopharyngeal colonisation.
不可分型流感嗜血杆菌（NTHi）是一种重要的呼吸道病原体，可引发多种感染，这些感染共同构成了巨大的健康和社会经济负担。这些感染的临床病程很大程度上取决于NTHi与宿主呼吸道上皮细胞的相互作用，因此，破坏其定植和侵袭的方法可能具有显著的治疗潜力。NTHi的存活、与宿主细胞的成功相互作用以及发病机制都依赖于其摄取宿主来源血红素的能力。此前，我们利用一种密切相关的竞争细菌（Hh）证明了利用这种对血红素的依赖性所具有的治疗潜力。能够产生新型血红素结合蛋白血青素（Hpl）的Hh菌株在肉汤共培养环境中通过限制NTHi获取血红素而具有强大的抑制活性。在此，我们将这项工作扩展到更接近人类呼吸道上皮的细胞培养模型，并表明高表达水平的Hh菌株可保护上皮细胞系单层免受NTHi的黏附和侵袭。抑制活性取决于Hpl的产生水平，NTHi刺激和鼻咽细胞暴露可刺激Hpl的产生。如果这些保护作用能够转化为体内应用，那么产生Hpl的Hh可能通过抑制必要的鼻咽定植而对NTHi感染具有益生菌效用。
