Exploiting the struggle for haem: A new respiratory probiotic candidate?
Atto, B and Kunde, D and Latham, R and Gell, D and Tristram, S, Exploiting the struggle for haem: A new respiratory probiotic candidate?, Australian Society for Microbiology Annual Scientific Meeting, 30 June - 1 July, Adelaide, South Australia (2019) [Conference Extract]
Nontypeable Haemophilus influenzae (NTHi) is a leading causative organism of opportunistic upper and lower respiratory tract infections, including otitis media, and exacerbations of chronic obstructive pulmonary disease. The rapid development of antibiotic resistance has complicated treatment, with infections frequently proving refractory to first- and second-line antibiotics. Development of preventative vaccination strategies has also proven unsuccessful. An alternative approach may be probiotic therapy that prevents nasopharyngeal colonisation, the prerequisite step of NTHi infection.
Newly discovered strains of the closely related, Haemophilus haemolyticus (Hh) present a promising probiotic candidate. These strains of Hh not only share the nasopharyngeal niche, but also produce a novel inhibitory substance, hemophilin (HPL) that restricts the growth of NTHi in vitro. Ongoing research indicates the inhibitory effect of HPL is due to its capacity to bind haem and limit the organismís access to the essential growth factor. Disruption of haem acquisition has previously been shown to significantly dampen the pathogenic capabilities of NTHi.
This research aims to determine the therapeutic potential of HPL-producing strains of Hh (Hh-HPL) in the prevention of NTHi infections through both in vitro and in vivo investigations. Data from oropharyngeal swabs of 150 healthy adults demonstrates a potential protective benefit against NTHi colonisation in individuals carrying Hh-HPL. The incidence and density of NTHi carriage was reduced by 52% and 68% in individuals co-colonised with Hh-HPL, respectively. This potential protective benefit was further explored using short-term in vitro competition studies. The growth rate of NTHi was significantly reduced by 66-84% (p < 0.0001) when co-cultured with Hh-HPL, but not Hh strains unable to produce HPL. Interestingly, exposure to NTHi increased the growth rate of Hh-HPL by 44-66% (p < 0.0001). The competitive advantage of Hh-HPL was also maintained during long-term fitness studies. This preliminary data shows that Hh-HPL may be a potential probiotic candidate for the prevention of NTHi infections.