HmuY differentially participates in heme acquisition compared to the and hemophore-like proteins.

Introduction: and 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 Hmu system, with a leading role played by the hemophore-like HmuY (HmuY) protein.

Methods: Theoretical analysis of selected HmuY proteins and spectrophotometric methods were employed to determine the heme-binding mode of the HmuY homolog (HmuY) and its ability to sequester heme. Growth phenotype and gene expression analysis of were employed to reveal the importance of the HmuY and Hmu system for this bacterium.

Results: Unlike in , where HmuY uses two histidines for heme-iron coordination, other known HmuY homologs use two methionines in this process. HmuY is the first characterized representative of the HmuY family that binds heme using a histidine-methionine pair. It allows HmuY to sequester heme directly from serum albumin and HmuY, the HmuY homolog which uses two methionines for heme-iron coordination. In contrast to HmuY, which sequesters heme directly from methemoglobin, HmuY may bind heme only after the proteolytic digestion of hemoglobin.

Conclusions: We hypothesize that differences in components of the Hmu system and structure-based properties of HmuY proteins may evolved allowing different adaptations of species to the changing host environment. This may add to the superior virulence potential of over other members of the Bacteroidota phylum.