title: Histoplasma capsulatum heat-shock 60 orchestrates the adaptation of the fungus to temperature stress.
abstract: Heat shock proteins (Hsps) are among the most widely distributed and evolutionary conserved proteins. Hsps are essential regulators of diverse constitutive metabolic processes and are markedly upregulated during stress. A 62 kDa Hsp (Hsp60) of Histoplasma capsulatum (Hc) is an immunodominant antigen and the major surface ligand to CR3 receptors on macrophages. However little is known about the function of this protein within the fungus. We characterized Hc Hsp60-protein interactions under different temperature to gain insights of its additional functions oncell wall dynamism, heat stress and pathogenesis. We conducted co-immunoprecipitations with antibodies to Hc Hsp60 using cytoplasmic and cell wall extracts. Interacting proteins were identified by shotgun proteomics. For the cell wall, 84 common interactions were identified among the 3 growth conditions, including proteins involved in heat-shock response, sugar and amino acid/protein metabolism and cell signaling. Unique interactions were found at each temperature [30°C (81 proteins), 37°C (14) and 37/40°C (47)]. There were fewer unique interactions in cytoplasm [30°C (6), 37°C (25) and 37/40°C (39)] and four common interactions, including additional Hsps and other known virulence factors. These results show the complexity of Hsp60 function and provide insights into Hc biology, which may lead to new avenues for the management of histoplasmosis.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, United States of America.
authors.forename: Allan Jefferson
authors.initials: AJ
authors.lastname: Guimarães
authors.forename: Ernesto S
authors.initials: ES
authors.lastname: Nakayasu
authors.forename: Tiago J P
authors.initials: TJ
authors.lastname: Sobreira
authors.forename: Radames J B
authors.initials: RJ
authors.lastname: Cordero
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Igor C
authors.initials: IC
authors.lastname: Almeida
authors.forename: Joshua Daniel
authors.initials: JD
authors.lastname: Nosanchuk
mesh_terms: D000222:Adaptation, Physiological; D000911:Antibodies, Monoclonal / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism*; D018869:Heat-Shock Response; D006658:Histoplasma / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D047468:Immunoprecipitation; D042541:Intracellular Space / Q000378:metabolism; D021381:Protein Transport; D013379:Substrate Specificity; D013696:Temperature; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D018834:Chaperonin 60; D005656:Fungal Proteins