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A heme-binding protein produced by Haemophilus haemolyticus inhibits non-typeable Haemophilus influenzae

Latham, RD ORCID: 0000-0002-6621-1949, Torrado, M, Atto, B, Walshe, JL, Wilson, R ORCID: 0000-0003-0152-4394, Guss, JM, Mackay, JP, Tristram, S ORCID: 0000-0002-8485-0322 and Gell, DA ORCID: 0000-0003-0382-1181 2019 , 'A heme-binding protein produced by Haemophilus haemolyticus inhibits non-typeable Haemophilus influenzae' , Molecular Microbiology , pp. 1-18 , doi: 10.1111/mmi.14426.

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Abstract

Commensal bacteria serve as an important line of defense against colonisation byopportunisitic pathogens, but the underlying molecular mechanisms remain poorlyexplored. Here, we show that strains of a commensal bacterium, Haemophilus haemolyticus, make hemophilin, a heme-binding protein that inhibits growth of the opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) in culture. We purifiedthe NTHi-inhibitory protein from H. haemolyticus and identified the hemophilin geneusing proteomics and a gene knockout. An x-ray crystal structure of recombinant hemophilin shows that the protein does not belong to any of the known heme-bindingprotein folds, suggesting that it evolved independently. Biochemical characterisationshows that heme can be captured in the ferrous or ferric state, and with a variety ofsmall heme-ligands bound, suggesting that hemophilin could function under a rangeof physiological conditions. Hemophilin knockout bacteria show a limited capacity toutilise free heme for growth. Our data suggest that hemophilin is a hemophore andthat inhibition of NTHi occurs by heme starvation, raising the possibility that competition from hemophilin-producing H. haemolyticus could antagonise NTHi colonisation in the respiratory tract.

Item Type: Article
Authors/Creators:Latham, RD and Torrado, M and Atto, B and Walshe, JL and Wilson, R and Guss, JM and Mackay, JP and Tristram, S and Gell, DA
Keywords: <i>Haemophilus haemolyticus</i>, hemophore, hemophilin, non-typeable <i>Haemophilus influenzae</i> (NTHi)
Journal or Publication Title: Molecular Microbiology
Publisher: Blackwell Publishing Ltd
ISSN: 0950-382X
DOI / ID Number: 10.1111/mmi.14426
Copyright Information:

© 2019 John Wiley & Sons Ltd

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