Silvio Ragozzino, Daniel Salete-Granado, Luis-Antonio Corchete, María-Paz Vaquero-Herrero, Edgar Bernardo, María Siller-Ruiz, Rebeca Sánchez González, Fabián Castaño-Romero, María-Ángeles Pérez-Nieto, Alicia García-Señán, Carlos Gutiérrez-Cerrajero, Cristina Carbonell, Jorge-Luis Torres, Rogelio González-Sarmiento, Guadalupe Sabio, Inmaculada García-García, Hugo-Guillermo Ternavasio-de la Vega, Maura Rojas-Pirela & Miguel Marcos.
Objectives: Analyze miRNA and mRNA expression in patients with bloodstream infection (BSI) caused by Candida albicans (CA) and non-albicans Candida spp. (CNA).
Patients/methods: We prospectively enrolled 20 adults with candidemia (10 CA and 10 CNA) and 22 hospitalized controls without sepsis but with comparable comorbidities. miRNA and mRNA expression were determined by next-generation sequencing (NGS), and differentially expressed miRNAs were validated by qPCR. Integrated miRNA–mRNA and KEGG/Reactome enrichment analyses were used to predict miRNA targets and identify perturbed pathways.
Results: NGS detected seven dysregulated miRNAs in CA vs. controls. qPCR confirmed marked overexpression of miR-125a-5p and miR-99b-5p in CA compared with CNA and controls. No miRNAs were differentially expressed between the CNA and control groups. RNA-Seq revealed that 22, 111, and 152 genes were differentially expressed in CA vs. controls, CNA vs. controls, and CA vs. CNA, respectively. Enrichment analysis highlighted cell-cycle and DNA-replication programs in both species groups, while CA uniquely affected histidine/phenylalanine metabolism. Integrated mapping linked upregulated miR-125a-5p to repression of pro-apoptotic and immune-modulatory genes, whereas miR-99b-5p targeted cell-cycle checkpoint genes.
Conclusions: Overexpression of miR-125a-5p and miR-99b-5p in whole blood may discriminate C. albicans candidemia. These miRNAs are promising rapid biomarkers and targets for antifungal therapy.
