关键词: HmuY Porphyromonas endodontalis Porphyromonas gingivalis Tannerella forsythia heme hemophore-like protein

Mesh : Heme / metabolism Porphyromonas gingivalis / metabolism genetics Tannerella forsythia / metabolism genetics Bacterial Proteins / metabolism genetics Porphyromonas endodontalis / metabolism genetics Humans Gene Expression Regulation, Bacterial Protein Binding Iron / metabolism

来  源:   DOI:10.3389/fcimb.2024.1421018   PDF(Pubmed)

Abstract:
UNASSIGNED: Porphyromonas gingivalis and Porphyromonas endodontalis belong to the Bacteroidota phylum. Both species inhabit the oral cavity and can be associated with periodontal diseases. To survive, they must uptake heme from the host as an iron and protoporphyrin IX source. Among the best-characterized heme acquisition systems identified in members of the Bacteroidota phylum is the P. gingivalis Hmu system, with a leading role played by the hemophore-like HmuY (HmuYPg) protein.
UNASSIGNED: Theoretical analysis of selected HmuY proteins and spectrophotometric methods were employed to determine the heme-binding mode of the P. endodontalis HmuY homolog (HmuYPe) and its ability to sequester heme. Growth phenotype and gene expression analysis of P. endodontalis were employed to reveal the importance of the HmuYPe and Hmu system for this bacterium.
UNASSIGNED: Unlike in P. gingivalis, where HmuYPg uses two histidines for heme-iron coordination, other known HmuY homologs use two methionines in this process. P. endodontalis HmuYPe is the first characterized representative of the HmuY family that binds heme using a histidine-methionine pair. It allows HmuYPe to sequester heme directly from serum albumin and Tannerella forsythia HmuYTf, the HmuY homolog which uses two methionines for heme-iron coordination. In contrast to HmuYPg, which sequesters heme directly from methemoglobin, HmuYPe may bind heme only after the proteolytic digestion of hemoglobin.
UNASSIGNED: We hypothesize that differences in components of the Hmu system and structure-based properties of HmuY proteins may evolved allowing different adaptations of Porphyromonas species to the changing host environment. This may add to the superior virulence potential of P. gingivalis over other members of the Bacteroidota phylum.
摘要:
牙龈卟啉单胞菌和根管卟啉单胞菌属于类杆菌门。这两种物种都栖息在口腔中,并且可能与牙周病有关。为了生存,它们必须从宿主中摄取血红素作为铁和原卟啉IX来源。在类杆菌门成员中鉴定出的特征最好的血红素采集系统是牙龈卟啉单胞菌Hmu系统,由血细胞样HmuY(HmuYPg)蛋白起主导作用。
选择的HmuY蛋白的理论分析和分光光度法用于确定牙周假单胞菌HmuY同系物(HmuYPe)的血红素结合模式及其螯合血红素的能力。采用牙髓多糖的生长表型和基因表达分析来揭示HmuYPe和Hmu系统对该细菌的重要性。
与牙龈卟啉单胞菌不同,HmuYPg使用两个组氨酸进行血红素-铁协调,其他已知的HmuY同系物在此过程中使用两种蛋氨酸。牙髓假单胞菌HmuYPe是使用组氨酸-甲硫氨酸对结合血红素的HmuY家族的第一个表征代表。它允许HmuYPe直接从血清白蛋白和连翘单纳菌HmuYTf中分离血红素,HmuY同系物,使用两个蛋氨酸进行血红素-铁配位。与HmuYPg相比,从高铁血红蛋白中直接螯合血红素,HmuYPe可能仅在血红蛋白的蛋白水解消化后结合血红素。
我们假设Hmu系统的组成部分和HmuY蛋白的基于结构的特性的差异可能会进化,从而使卟啉单胞菌物种适应不断变化的宿主环境。这可能增加牙龈卟啉单胞菌优于类杆菌门的其他成员的毒力潜力。
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