Hfe Permease and Haemophilus influenzae Manganese Homeostasis.

Autor: Ganio K; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia., Nasreen M; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia., Yang Z; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia., Maunders EA; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia., Luo Z; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia.; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia., Hossain SI; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; School of Life Sciences, University of Technology Sydney, Ultimo, New South Wales 2007, Australia., Ngu DHY; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia.; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia., Ellis D; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia., Gu J; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia., Neville SL; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia., Wilksch J; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia., Gunn AP; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia., Whittall JJ; School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia., Kobe B; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia.; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia., Deplazes E; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; School of Life Sciences, University of Technology Sydney, Ultimo, New South Wales 2007, Australia., Kappler U; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, St Lucia, Queensland 4072, Australia., McDevitt CA; Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Jazyk: angličtina
Zdroj: ACS infectious diseases [ACS Infect Dis] 2024 Feb 09; Vol. 10 (2), pp. 436-452. Date of Electronic Publication: 2024 Jan 19.
DOI: 10.1021/acsinfecdis.3c00407
Abstrakt: 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.
Databáze: MEDLINE