SUMNARYHeme(铁原卟啉IX,FePPIX)是宿主相关致病菌铁和PPIX的主要来源,包括拟杆菌(以前的拟杆菌)门的成员。牙龈卟啉单胞菌,主要的口腔病原体,使用独特的血红素摄取(Hmu)系统,包含血团样蛋白,被指定为小说HmuY家族的第一位成员。与古典相比,革兰氏阴性菌利用的分泌血团或革兰氏阳性菌利用的基于近铁转运蛋白结构域的血团,HmuY家族包含在进化过程中经历多样化的结构相似的蛋白质。最好的特征是牙龈卟啉单胞菌HmuY及其来自连翘坦纳菌(Tfo)的同源物,介间普氏菌(PinO和PinA),寻常拟杆菌(Bvu),和脆弱拟杆菌(Bfra,Bfrb,和BfRC)。与牙龈卟啉单胞菌HmuY中协调血红素铁的两个组氨酸残基相反,Tfo,皮诺,皮纳,Bvu,和BfrA优先使用两个甲硫氨酸残基。有趣的是,Bfrb,尽管蛋氨酸残基保守,结合PPIX环没有铁配位。BfrC既不结合血红素也不结合PPIX,这与HmuY家族的其他成员使用的保守组氨酸或甲硫氨酸残基的缺乏相一致。HmuY与HmuY家族的其他成员竞争血红素结合和从宿主血液蛋白中螯合血红素以增加牙龈卟啉单胞菌的竞争力。HmuY参与宿主免疫反应证实了它与牙龈卟啉单胞菌存活的相关性,以及它不仅在口腔微生物组中,而且在肠道微生物组或其他宿主生态位诱导菌群失调的能力,导致局部受伤和合并症。
CONCLUSIONS: Heme (iron protoporphyrin IX, FePPIX) is the main source of iron and PPIX for host-associated pathogenic bacteria, including members of the Bacteroidota (formerly Bacteroidetes) phylum. Porphyromonas gingivalis, a keystone oral pathogen, uses a unique heme uptake (Hmu) system, comprising a hemophore-like protein, designated as the first member of the novel HmuY family. Compared to classical, secreted hemophores utilized by Gram-negative bacteria or near-iron transporter domain-based hemophores utilized by Gram-positive bacteria, the HmuY family comprises structurally similar proteins that have undergone diversification during evolution. The best characterized are P. gingivalis HmuY and its homologs from Tannerella forsythia (Tfo), Prevotella intermedia (PinO and PinA), Bacteroides vulgatus (Bvu), and Bacteroides fragilis (BfrA, BfrB, and BfrC). In contrast to the two histidine residues coordinating heme iron in P. gingivalis HmuY, Tfo, PinO, PinA, Bvu, and BfrA preferentially use two methionine residues. Interestingly, BfrB, despite conserved methionine residue, binds the PPIX ring without iron coordination. BfrC binds neither heme nor PPIX in keeping with the lack of conserved histidine or methionine residues used by other members of the HmuY family. HmuY competes for heme binding and heme sequestration from host hemoproteins with other members of the HmuY family to increase P. gingivalis competitiveness. The participation of HmuY in the host immune response confirms its relevance in relation to the survival of P. gingivalis and its ability to induce dysbiosis not only in the oral microbiome but also in the gut microbiome or other host niches, leading to local injuries and involvement in comorbidities.