Ganio Katherine, Nasreen Marufa, Yang Zihao, Maunders Eve A, Luo Zhenyao, Hossain Sheikh Imamul, Ngu Dalton H Y, Ellis Daniel, Gu Jin, Neville Stephanie L, Wilksch Jonathan, Gunn Adam P, Whittall Jonathan J, Kobe Boštjan, Deplazes Evelyne, Kappler Ulrike, McDevitt Christopher A
Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
ACS Infect Dis. 2024 Feb 9;10(2):436-452. doi: 10.1021/acsinfecdis.3c00407. Epub 2024 Jan 19.
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 , a gene previously linked to iron import, is essential for manganese recruitment 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 reduced 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 manganese acquisition and virulence attributes. High conservation of the permease in species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.
是人类上呼吸道的一种共生菌，它能够感染多种宿主生态位，至少部分原因在于其耐受内源性和宿主介导的氧化应激的能力。在此，我们表明，一个先前与铁摄取相关的基因，对于HfeBCD转运体募集锰至关重要。结构分析表明，HfeA中的金属结合采用了一种独特机制，该机制涉及蛋白质C末端叶的大幅旋转。该基因的破坏减少了锰的获取，并与有氧条件下生长减少、锰超氧化物歧化酶活性受损、巨噬细胞内存活率降低以及超氧化物存在时生物膜产生的变化有关。总体而言，这项工作表明HfeA有助于锰的获取和毒力特性。该通透酶在物种中的高度保守性表明它可能在其他致病性巴斯德氏菌科中发挥类似作用。
