RT Journal Article T1 The Combination of Iron and Copper Increases Pathogenicity and Induces Proteins Related to the Main Virulence Factors in Clinical Isolates of Cryptococcus neoformans var. grubii A1 Vélez, Nórida A1 Monteoliva, Lucía A1 Sánchez Quitian, Zilpa Adriana A1 Amador García, Ahinara A1 García Rodas, Rocío A1 Ceballos Garzón, Andrés A1 Gil García, Concha A1 Escandón, Patricia A1 Zaragoza, Óscar A1 Parra Giraldo, Claudia Marcela AB In fungi, metals are associated with the expression of virulence factors. However, it is unclear whether the uptake of metals affects their pathogenicity. This study aimed to evaluate the effect of iron/copper in modulating pathogenicity and proteomic response in two clinical isolates of C. neoformans with high and low pathogenicity. Methods: In both isolates, the effect of 50 µM iron and 500 µM copper on pathogenicity, capsule induction, and melanin production was evaluated. We then performed a quantitative proteomic analysis of cytoplasmic extracts exposed to that combination. Finally, the effect on pathogenicity by iron and copper was evaluated in eight additional isolates. Results: In both isolates, the combination of iron and copper increased pathogenicity, capsule size, and melanin production. Regarding proteomic data, proteins with increased levels after iron and copper exposure were related to biological processes such as cell stress, vesicular traffic (Ap1, Vps35), cell wall structure (Och1, Ccr4, Gsk3), melanin biosynthesis (Hem15, Mln2), DNA repair (Chk1), protein transport (Mms2), SUMOylation (Uba2), and mitochondrial transport (Atm1). Increased pathogenicity by exposure to metal combination was also confirmed in 90% of the eight isolates. Conclusions: The combination of these metals enhances pathogenicity and increases the abundance of proteins related to the main virulence factors. PB MPDI SN 2309-608X YR 2022 FD 2022-12-31 LK https://hdl.handle.net/20.500.14352/72504 UL https://hdl.handle.net/20.500.14352/72504 LA eng NO Ministerio de Ciencia e Innovación (MICINN) NO Ministerio de Ciencia e Innovación (MICINN)/ISCII NO Research Vice Presidency of the Pontificia Universidad Javeriana in Bogotá, Colombia NO I DS Docta Complutense RD 7 may 2024