Screening of potential genes contributing to the macrocycle drug resistance of C. albicans via microarray analysis

Abstract

The aim of the present study was to investigate the potential genes involved in drug resistance of Candida albicans (C. albicans) by performing microarray analysis. The gene expression profile of GSE65396 was downloaded from the Gene Expression Omnibus, including a control, 15-min and 45-min macrocyclic compound RF59-treated group with three repeats for each. Following preprocessing using RAM, the differentially expressed genes (DEGs) were screened using the Limma package. Subsequently, the Kyoto Encyclopedia of Genes and Genomes pathways of these genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery. Based on interactions estimated by the Search Tool for Retrieval of Interacting Gene, the protein-protein interaction (PPI) network was visualized using Cytoscape. Subnetwork analysis was performed using ReactomeFI. A total of 154 upregulated and 27 downregulated DEGs were identified in the 15-min treated group, compared with the control, and 235 upregulated and 233 downregulated DEGs were identified in the 45-min treated group, compared with the control. The upregulated DEGs were significantly enriched in the ribosome pathway. Based on the PPI network, PRP5, RCL1, NOP13, NOP4 and MRT4 were the top five nodes in the 15-min treated comparison. GIS2, URA3, NOP58, ELP3 and PLP7 were the top five nodes in the 45-min treated comparison, and its subnetwork was significantly enriched in the ribosome pathway. The macrocyclic compound RF59 had a notable effect on the ribosome and its associated pathways of C. albicans. RCL1, NOP4, MRT4, GIS2 and NOP58 may be important in RF59-resistance.

Roles of Nucleolar Factor RCL1 in Itraconazole Resistance of Clinical Candida albicans Under Different Stress Conditions

“…23 Moreover, our previous study demonstrated 774 a significant increase in RCL1 expression in C. albicans upon treatment with RF59, a macrocyclic compound. 17 These findings suggest that RCL1 contributes to the improved the physiological status of C. albicans. However, the expression 1 changes of RCL in C. albicans have not been thoroughly investigated.…”

“…29 The viral stress gene RCL1 encoding a nucleolar protein is essential for 18S rRNA in ribosome biosynthesis. 15,17 Moreover, Enjalbert et al verified that RCL1 is the main regulatory factor in C. albicans under various stress conditions, including oxidation and heavy metal stress. 18 As C. albicans is well known for its characteristic dimorphism, existing as both a yeast and mycelium form, different environmental stimuli, such as a neutral pH value, 25°C and 5% CO 2 can induce changes in its dimorphism of C. albicans.…”

Investigation of Gene Networks in Three Components of Immune System Provides Novel Insights into Immune Response Mechanisms against Edwardsiella tarda Infection in Paralichthys olivaceus

“…These complexes played a pivotal role in the modification and processing of pre-ribosomal RNA [51]. nop58, a primary interacting partner of Box C/D RNA, facilitated gene methylation upon binding, thus modulating the expression of immune-related genes [52,53].…”

mRNA Turnover Protein 4 Is Vital for Fungal Pathogenicity and Response to Oxidative Stress in Sclerotinia sclerotiorum

“…It was shown that the subcellular localization of human MRT4 is regulated by the C-terminal region under stress [ 21 ]. MRT4 was significantly up-regulated within 15 min when screening the possible genes related to the drug resistance of Candida albicans [ 22 ], indicating that it may regulate the effectiveness of drugs.…”