MicroRNA whole-blood profiling in hospitalized patients with candidemia identified miR-125a-5p and miR-99b-5p as potential biomarkers for Candida albicans bloodstream infection.

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.