Atto Brianna, Gell David A, Marsh Robyn, Tristram Stephen
School of Health Sciences, University of Tasmania, Launceston, TAS, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Front Cell Infect Microbiol. 2025 May 15;15:1548048. doi: 10.3389/fcimb.2025.1548048. eCollection 2025.
Nontypeable (NTHi) is a major respiratory pathogen that imposes a substantial disease burden, globally. Further amplifying the burden of NTHi-associated infections is the rapidly expanding spectrum and prevalence of antibiotic resistance, and the lack of an effective vaccination strategy. In 2017, the World Health Organization list of "priority pathogens", highlighted the urgent need for new therapeutic agents against NTHi. Consequently, alternative preventative or treatment approaches that do not rely on antibiotic susceptibility or stable vaccine targets are becoming more attractive. The nutritional dependency for haem/iron at all stages of NTHi pathogenesis exposes a vulnerability that may be exploited for the development of such therapies. This review explores the role of haem/iron in all facets of NTHi pathogenesis, the host-bacterial competition for this vital nutrient, and the therapeutic potential of strategies that interfere with its acquisition.
不可分型流感嗜血杆菌(NTHi)是一种主要的呼吸道病原体,在全球范围内造成了沉重的疾病负担。NTHi相关感染负担的进一步加重是由于抗生素耐药性的迅速扩大和流行,以及缺乏有效的疫苗接种策略。2017年,世界卫生组织的“优先病原体”清单强调了迫切需要针对NTHi的新型治疗药物。因此,不依赖抗生素敏感性或稳定疫苗靶点的替代预防或治疗方法正变得更具吸引力。NTHi发病机制所有阶段对血红素/铁的营养依赖性暴露了一个弱点,可利用这一弱点开发此类疗法。本综述探讨了血红素/铁在NTHi发病机制各个方面的作用、宿主与细菌对这种重要营养素的竞争,以及干扰其获取的策略的治疗潜力。