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

Citation

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, A heme-binding protein produced by Haemophilus haemolyticus inhibits non-typeable Haemophilus influenzae, Molecular Microbiology pp. 1-18. ISSN 0950-382X (2019) [Refereed Article]

Copyright Statement

2019 John Wiley & Sons Ltd

DOI: doi:10.1111/mmi.14426

Abstract

Commensal bacteria serve as an important line of defense against colonisation by opportunisitic pathogens, but the underlying molecular mechanisms remain poorly explored. 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 purified the NTHi-inhibitory protein from H. haemolyticus and identified the hemophilin gene using 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-binding protein folds, suggesting that it evolved independently. Biochemical characterisation shows that heme can be captured in the ferrous or ferric state, and with a variety of small heme-ligands bound, suggesting that hemophilin could function under a range of physiological conditions. Hemophilin knockout bacteria show a limited capacity to utilise free heme for growth. Our data suggest that hemophilin is a hemophore and that 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 Details

Item Type:Refereed Article
Keywords:<i>Haemophilus haemolyticus</i>, hemophore, hemophilin, non-typeable <i>Haemophilus influenzae</i> (NTHi)
Research Division:Medical and Health Sciences
Research Group:Medical Microbiology
Research Field:Medical Bacteriology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Infectious Diseases
UTAS Author:Latham, RD (Mr Roger Latham)
UTAS Author:Atto, B (Miss Brianna Atto)
UTAS Author:Wilson, R (Dr Richard Wilson)
UTAS Author:Tristram, S (Dr Stephen Tristram)
UTAS Author:Gell, DA (Dr David Gell)
ID Code:136378
Year Published:2019
Deposited By:Health Sciences
Deposited On:2019-12-17
Last Modified:2020-05-19
Downloads:0

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