Exploiting the struggle for haem: a novel therapeutic approach against Haemophilus influenzae

Abstract

Over the past decade, nontypeable Haemophilus influenzae (NTHi) has gained recognition as a major opportunistic pathogen of the respiratory tract that imposes a substantial global burden of disease, owing to a high rate of morbidity and ensuing complications. Further amplifying the global impact of NTHi infections is the increasing spectrum and prevalence of antibiotic resistance, leading to higher rates of treatment failure with first- and second-line antibiotics regimes. The threat of antibiotic resistance was recognised by the World Health Organization in 2017, listing NTHi as a priority pathogen for which new therapies are urgently needed. Despite significant efforts, there are currently no effective vaccine strategies available that can slow the growing burden of NTHi disease. Consequently, alternative preventative or therapeutic approaches that do not rely on antibiotic susceptibility or stable vaccine targets are becoming more attractive. The nutritional dependency for haem at all stages of NTHi pathogenesis exposes a vulnerability that may be exploited for the development of such therapies. This article will discuss the therapeutic potential of strategies that limit NTHi access to this vital nutrient, with particular focus on a novel bacteriotherapeutic approach under development.