Hfe Permease and Haemophilus influenzae Manganese Homeostasis.

Ganio, K; Nasreen, M; Yang, Z; Maunders, EA; Luo, Z; Hossain, SI; Ngu, DHY; Ellis, D; Gu, J; Neville, SL; Wilksch, J; Gunn, AP; Whittall, JJ; Kobe, B; Deplazes, E; Kappler, U; McDevitt, CA

Hfe Permease and Haemophilus influenzae Manganese Homeostasis.

Ganio, K Nasreen, M Yang, Z Maunders, EA Luo, Z Hossain, SI Ngu, DHY Ellis, D Gu, J Neville, SL Wilksch, J Gunn, AP Whittall, JJ Kobe, B Deplazes, E

Kappler, U McDevitt, CA

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: ACS Infect Dis, 2024, 10, (2), pp. 436-452
Issue Date:: 2024-02-09

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Field	Value	Language
dc.contributor.author	Ganio, K
dc.contributor.author	Nasreen, M
dc.contributor.author	Yang, Z
dc.contributor.author	Maunders, EA
dc.contributor.author	Luo, Z
dc.contributor.author	Hossain, SI
dc.contributor.author	Ngu, DHY
dc.contributor.author	Ellis, D
dc.contributor.author	Gu, J
dc.contributor.author	Neville, SL
dc.contributor.author	Wilksch, J
dc.contributor.author	Gunn, AP
dc.contributor.author	Whittall, JJ
dc.contributor.author	Kobe, B
dc.contributor.author	Deplazes, E https://orcid.org/0000-0003-2052-5536
dc.contributor.author	Kappler, U
dc.contributor.author	McDevitt, CA
dc.date.accessioned	2024-11-07T02:52:04Z
dc.date.available	2024-11-07T02:52:04Z
dc.date.issued	2024-02-09
dc.identifier.citation	ACS Infect Dis, 2024, 10, (2), pp. 436-452
dc.identifier.issn	2373-8227
dc.identifier.issn	2373-8227
dc.identifier.uri	http://hdl.handle.net/10453/181791
dc.description.abstract	Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation	http://purl.org/au-research/grants/nhmrc/1122582
dc.relation.ispartof	ACS Infect Dis
dc.relation.isbasedon	10.1021/acsinfecdis.3c00407
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1108 Medical Microbiology
dc.subject.classification	3207 Medical microbiology
dc.subject.mesh	Humans
dc.subject.mesh	Haemophilus influenzae
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Manganese
dc.subject.mesh	Biofilms
dc.subject.mesh	Homeostasis
dc.subject.mesh	Humans
dc.subject.mesh	Biofilms
dc.subject.mesh	Haemophilus influenzae
dc.subject.mesh	Manganese
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Homeostasis
dc.subject.mesh	Humans
dc.subject.mesh	Haemophilus influenzae
dc.subject.mesh	Membrane Transport Proteins
dc.subject.mesh	Manganese
dc.subject.mesh	Biofilms
dc.subject.mesh	Homeostasis
dc.title	Hfe Permease and Haemophilus influenzae Manganese Homeostasis.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	United States
utslib.for	1108 Medical Microbiology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Mechanical and Mechatronic Engineering
utslib.copyright.status	closed_access	*
dc.date.updated	2024-11-07T02:52:02Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	2

Abstract:

Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.

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http://hdl.handle.net/10453/181791