Śmiga Michał, Ślęzak Paulina, Tracz Michał, Cierpisz Patryk, Wagner Mateusz, Olczak Teresa
Laboratory of Medical Biology, Faculty of Biotechnology, University of Wrocław, 14A F. Joliot-Curie St., 50-383, Wrocław, Poland.
Laboratory of Protein Mass Spectrometry, Faculty of Biotechnology, University of Wrocław, 14A F. Joliot-Curie St., 50-383, Wrocław, Poland.
Sci Rep. 2024 Dec 28;14(1):31156. doi: 10.1038/s41598-024-82326-6.
Iron and heme are essential nutrients for all branches of life. Pathogenic members of the Bacteroidota phylum, including Porphyromonas gingivalis, do not synthesize heme and rely on host hemoproteins for heme as a source of iron and protoporphyrin IX. P. gingivalis is the main pathogen responsible for dysbiosis in the oral microbiome and the initiation and progression of chronic periodontitis. It utilizes Hmu and Hus systems for heme uptake, including HmuY and HusA hemophore-like proteins and their cognate HmuR and HusB TonB-dependent outer membrane heme receptors. Although the mechanisms of heme uptake are relatively well characterized in P. gingivalis, little is known about the importance of heme uptake systems in heme and iron homeostasis and virulence. Therefore, this work aimed to investigate these mechanisms in detail. We characterized the P. gingivalis double mutant strain deficient in functional hmuY and hmuR or husA and husB genes. Global gene expression and phenotypic analyses revealed that the Hmu system significantly influences heme homeostasis, confirming its main role in heme supply. Both systems, particularly the Hus system, affect the virulence of P. gingivalis. Our results demonstrate the diverse role of Hmu and Hus systems in P. gingivalis heme and iron homeostasis and virulence.
铁和血红素是所有生命分支所必需的营养素。拟杆菌门的致病成员，包括牙龈卟啉单胞菌，不能合成血红素，而是依赖宿主血红蛋白来获取作为铁和原卟啉IX来源的血红素。牙龈卟啉单胞菌是导致口腔微生物群失调以及慢性牙周炎起始和进展的主要病原体。它利用Hmu和Hus系统摄取血红素，包括HmuY和HusA类血红蛋白蛋白及其同源的HmuR和HusB TonB依赖性外膜血红素受体。尽管牙龈卟啉单胞菌摄取血红素的机制已得到相对充分的表征，但关于血红素摄取系统在血红素和铁稳态以及毒力中的重要性却知之甚少。因此，这项工作旨在详细研究这些机制。我们对缺乏功能性hmuY和hmuR或husA和husB基因的牙龈卟啉单胞菌双突变株进行了表征。全局基因表达和表型分析表明，Hmu系统显著影响血红素稳态，证实了其在血红素供应中的主要作用。这两个系统，特别是Hus系统，影响牙龈卟啉单胞菌的毒力。我们的结果证明了Hmu和Hus系统在牙龈卟啉单胞菌血红素和铁稳态以及毒力中的不同作用。
