Characterization of the transcriptional response of Candida parapsilosis to the antifungal peptide MAF-1A

Abstract

Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.

Early detection of Candida parapsilosis sepsis in peripheral blood as a result of cytografic changes on the Sysmex XN‐3000 hematology analyzer

“…Of these species, Candida parapsilosis is of particular importance, as they are able to form firm and persistent biofilms in central venous catheters in addition to other medical devices, thus threatening patients undergoing invasive medical procedures. 1,2 Accordingly, diagnostic support tools such as microscopic blood smear reviews (MBSR) and cytographic changes caused by yeasts in the counting channels of the automated hematology analyzers can be of great utility, since they can enable the rapid diagnosis of a fungemia when compared to the time-consuming blood cultures. 3,4 The cytographic information derived from the counting channels scattergrams of the Sysmex XN-3000 hematology analyzer may have a possible correlation with the morphological findings in the peripheral blood smear in cases of Candida parapsilosis sepsis.…”

Antimicrobial Peptides with Anti-Candida Activity

“…This peptide has shown a noteworthy antifungal effect [ 91 , 92 , 93 , 210 ]. MAF-1A induced a series of complex transcriptional responses to inhibit C. albicans growth, including the downregulation of ergosterol synthesis and ROS production [ 91 ].…”

“…MAF-1A induced a series of complex transcriptional responses to inhibit C. albicans growth, including the downregulation of ergosterol synthesis and ROS production [ 91 ]. Some transcriptional responses to MAF-1A were also studied in C. parapsilosis , showing that the membrane and some organelles, such as the mitochondria, were affected when the yeast was treated with this AMP [ 92 ]. Furthermore, MAF-1A also compromises the cell wall and binds to C. albicans nucleic acids [ 93 ].…”