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Haemophilin-producing strains of Haemophilus haemolyticus protect respiratory epithelia from NTHi colonisation and internalisation

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Atto, B, Kunde, D ORCID: 0000-0002-6513-032X, Gell, DA ORCID: 0000-0003-0382-1181 and Tristram, S ORCID: 0000-0002-8485-0322 2021 , 'Haemophilin-producing strains of Haemophilus haemolyticus protect respiratory epithelia from NTHi colonisation and internalisation' , Pathogens, vol. 10, no. 1 , pp. 1-15 , doi: 10.3390/pathogens10010029.

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Abstract

Nontypeable Haemophilus influenzae (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, Haemophilus haemolyticus (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 hpl 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.

Item Type: Article
Authors/Creators:Atto, B and Kunde, D and Gell, DA and Tristram, S
Keywords: Haemophilus haemolyticus, Haemophilus influenzae, haem, haem-binding protein, haemophilin, haemophore, host–cell interactions, respiratory infections, respiratory probiotic
Journal or Publication Title: Pathogens
Publisher: MDPI AG
ISSN: 2076-0817
DOI / ID Number: 10.3390/pathogens10010029
Copyright Information:

Copyright 2021 by the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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