Identification of a novel iron regulated staphylococcal surface protein with haptoglobin-haemoglobin binding activity

摘要: Staphylococcus aureus is an extremely adaptable pathogen causing a wide variety of infections. Staphylococcal surface proteins that directly interact with host extracellular greatly contribute to virulence and are involved in adhesion, immune escape nutrient acquisition. In our extensive search for highly immunogenic, vivo-expressed, staphylococcal proteins, previously, we identified novel member the family Gram-positive anchor motif predicted 895 amino acid long sequence. order determine ligand this LPXTG cell wall protein, employed affinity purification human plasma using recombinant form protein. Two-dimensional electrophoresis eluted haptoglobin as specific binding partner. Importantly, also observed when living S. cells were exposed biotin-labelled (Hp) FACS-based assay. Targeted deletion gene eliminated Hp-binding, function has not been attributed before. Based on these data specified protein receptor A (HarA). Similarly other receptors Gram-negative pathogens, HarA binds only Hp, but haptoglobin-haemoglobin complexes even higher affinity, demonstrated vitro assays. Employing mutants, was localized two homologous regions about 145 residues located within N-terminal part addition, expression strictly controlled by iron through iron-dependent transcriptional regulator Fur. propose can be added list factors most likely related