Abstract

Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections.

Highlights

  • Candida albicans (C. albicans) is the causative agent of candidiasis in humans that causes superficial as well as invasive infection [1]

  • The systemic candidiasis with the rise of C. albicans level in the bloodstream is most prevalent in fungal infected tissues; this menace has been increased in immunocompromised individuals [3]

  • Confirmation of C. albicans in blood samples

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Summary

Introduction

Candida albicans (C. albicans) is the causative agent of candidiasis in humans that causes superficial as well as invasive (systemic) infection [1]. The systemic candidiasis with the rise of C. albicans level in the bloodstream is most prevalent in fungal infected tissues; this menace has been increased in immunocompromised individuals [3]. Fungal spores can destruct sensitive lung tissues which lead to scar formation. Regulation of these physiological processes requires complex progressive modifications in epithelial cell biology, which is largely controlled by the expression of genetic elements [6]. The expression of small non-coding RNA molecules termed miRNAs is involved to coordinate regulation of expression [7] of at least 30% of human genes. MiRNAs are considered as master regulators of gene expressions [8]

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