Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
National Research Council Canada, Human Health Therapeutics (HHT) Research Center, Ottawa, ON, Canada.
Nat Commun. 2021 Nov 1;12(1):6270. doi: 10.1038/s41467-021-26545-9.
Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
营养物质获取系统通常对病原体在感染过程中的生长和存活至关重要,是有吸引力的治疗靶点。在这里,我们研究了机会性病原体鲍曼不动杆菌获取血红素所需的蛋白质机制。我们表明,hemO 基因座(包含编码血红素降解酶的基因)是从血红蛋白和血清白蛋白中高亲和力获取血红素所必需的。hemO 基因座包含一个编码血红素清除剂(HphA)的基因,该基因由 Slam 蛋白分泌。此外,血红素摄取依赖于 TonB 依赖性受体(HphR),该受体对于在肺部感染的小鼠模型中的存活和/或传播到脉管系统是重要的。我们的结果表明,鲍曼不动杆菌使用双组分受体系统从宿主血红素储库中获取血红素。