title: Apoptosis of Candida albicans during the Interaction with Murine Macrophages: Proteomics and Cell-Death Marker Monitoring.
abstract: Macrophages may induce fungal apoptosis to fight against C. albicans, as previously hypothesized by our group. To confirm this hypothesis, we analyzed proteins from C. albicans cells after 3 h of interaction with macrophages using two quantitative proteomic approaches. A total of 51 and 97 proteins were identified as differentially expressed by DIGE and iTRAQ, respectively. The proteins identified and quantified were different, with only seven in common, but classified in the same functional categories. The analyses of their functions indicated that an increase in the metabolism of amino acids and purine nucleotides were taking place, while the glycolysis and translation levels dropped after 3 h of interaction. Also, the response to oxidative stress and protein translation were reduced. In addition, seven substrates of metacaspase (Mca1) were identified (Cdc48, Fba1, Gpm1, Pmm1, Rct1, Ssb1, and Tal1) as decreased in abundance, plus 12 proteins previously described as related to apoptosis. Besides, the monitoring of apoptotic markers along 24 h of interaction (caspase-like activity, TUNEL assay, and the measurement of ROS and cell examination by transmission electron microscopy) revealed that apoptotic processes took place for 30% of the fungal cells, thus supporting the proteomic results and the hypothesis of macrophages killing C. albicans by apoptosis.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Cabezón
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Vital
authors.initials: V
authors.lastname: Vialás
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gil-Bona
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Reales-Calderón
authors.affiliation: Unidad de Proteómica, Universidad Complutense de Madrid-Parque Científico de Madrid (UCM-PCM) , 28040 Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Martínez-Gomariz
authors.affiliation: Unidad de Proteómica, Universidad Complutense de Madrid-Parque Científico de Madrid (UCM-PCM) , 28040 Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Gutiérrez-Blázquez
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Monteoliva
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Molero
authors.affiliation: Biosciences, University of Exeter , Geoffrey Pope Building, Exeter, Devon, EX4 4QD, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Ramsdale
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid , Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain.|Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Ctra. de Colmenar Viejo, 28034 Madrid, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Gil
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002176:Candida albicans / Q000166:cytology*; D015966:Gene Expression Regulation, Fungal / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D008264:Macrophages / Q000737:chemistry* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers
keywords: 2D-DIGE; Candida albicans; DNA fragmentation; apoptosis; iTRAQ; macrophages; metabolism; metacaspase