Journal article
Hfe Permease and Haemophilus influenzae Manganese Homeostasis
Katherine Ganio, Marufa Nasreen, Zihao Yang, Eve A Maunders, Zhenyao Luo, Sheikh Imamul Hossain, Dalton HY Ngu, Daniel Ellis, Jin Gu, Stephanie L Neville, Jonathan Wilksch, Adam P Gunn, Jonathan J Whittall, Boštjan Kobe, Evelyne Deplazes, Ulrike Kappler, Christopher A McDevitt
ACS Infectious Diseases | American Chemical Society | Published : 2024
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..
View full abstractRelated Projects (4)
Grants
Awarded by Australian Government
Funding Acknowledgements
We thank Dr Ama-Tawiah Essilfie for assistance with the murine experiments and Professor Alastair McEwan (University of Queensland, Australia) and Professor Megan Maher (University of Melbourne, Australia) for discussion and feedback on the manuscript. We acknowledge use and thank the staff of the Australian Synchrotron MX beamlines, the UQ-ROCX (University of Queensland Remote Operation Crystallization and X-ray Diffraction) Facility at the Centre for Microscopy and Microanalysis, and the Melbourne Mass Spectrometry and Proteomics Facility (MMSPF) at the Bio21 Molecular Science and Biotechnology Institute, the University of Melbourne. This research was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government and by resources provided by The Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia. This research was also undertaken using the LIEF HPC-GPGPU Facility hosted at the University of Melbourne. This Facility was established with the assistance of Australian Research Council (ARC) LIEF grant LE170100200. This work was supported by the National Health and Medical Research Council (NHMRC) grants 1071659 to B.K., 1122582 to C.A.M., 1180826 to B.K. and C.A.M, and 1158451 to U.K., A.G.M., and A-T.E. E.D. is a UTS Chancellor's Postdoctoral Fellow, B.K. is an ARC Laureate Fellow (FL180100109), and C.A.M. is an ARC Future Fellow (FT170100006). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.