Proteomic Analysis of Caspofungin-Induced Responses in Planktonic Cells and Biofilms of Candida albicans

Abstract

Candida albicans biofilms display markedly increased antifungal resistance, and the underlying mechanisms remain unclear. This study investigated the signature profiles of C. albicans planktonic cells and biofilms in response to caspofungin (CAS) by mass spectrometry-based shotgun proteomics. We found that C. albicans biofilms were twofold more resistant to CAS with reference to planktonic cells. Notably, 9.6% of C. albicans biofilm cells survived the lethal treatment of CAS (128 μg/ml), confirmed by LIVE/DEAD staining, confocal laser scanning microscopy (CLSM) and scanning electron microscopy analyses. The responses of C. albicans planktonic cells and biofilms to CAS treatment at respective minimum inhibitory concentrations (MICs) were assessed by high-throughput proteomics and bioinformatics approaches. There were 148 and 224 proteins with >twofold difference identified from the planktonic cells and biofilms, respectively. CAS treatment downregulated several cell wall- and oxidative stress-related proteins. Whereas, CAS-induced action was compensated by markedly increased expression of many other proteins involved in cell wall integrity and stress response (e.g., heat shock proteins). Moreover, considerable expression changes were identified in metabolism-associated proteins like glycolysis, tricarboxylic acid (TCA) cycle and ATP biosynthesis. Importantly, various key proteins for cell wall integrity, stress response and metabolic regulation (e.g., PIL1, LSP1, HSP90, ICL1, and MLS1) were exclusively enriched and implicated in C. albicans biofilms. This study demonstrates that C. albicans biofilms undergo highly complicated yet complex regulation of multiple cellular pathways in response to CAS. Signature proteins essential for modulating cell wall integrity, stress response and metabolic activities may account for the antifungal resistance of C. albicans biofilms.

Exposure of Candida parapsilosis to the silver(I) compound SBC3 induces alterations in the proteome and reduced virulence

“…Therefore, it has been applied to provide insight on the effect(s) of novel and conventional antifungal treatments. 105 – 108 The results presented here indicate that exposure of C. parapsilosis to SBC3 results in reductions in proteins associated with protein synthesis, amino acid synthesis, and respiration and in virulence as measured by the inhibition of adherence and biofilm formation. These findings provide a novel insight into the mode of action of SBC3 and encourage further research into this interesting antifungal agent.…”

Genomic and Molecular Identification of Genes Contributing to the Caspofungin Paradoxical Effect inAspergillus fumigatus

“…Further, the CPE – mutant showed an upregulation of ribosome biogenesis genes in the presence of caspofungin in comparison to the WT CPE + isolate ( 43 ). Transcriptomic and proteomic analysis of Candida albicans and Candida auris in the presence of caspofungin also showed an enrichment of differentially expressed genes and proteins involved in ribosomal function ( 82 – 84 ). The general interaction between caspofungin and ribosome biogenesis could represent a metabolic reshuffling in response to caspofungin, and dspC is an interesting candidate gene because of its close association with ribosome biogenesis ( 78 ).…”

Antifungal Activity, Synergism with Fluconazole or Amphotericin B and Potential Mechanism of Direct Current against Candida albicans Biofilms and Persisters

“…A well-characterized clinical isolate used in our previous studies, C. albicans BF-1, was selected for this study [ 5 , 19 ]. For broth culture, the yeast was incubated on yeast extract peptone dextrose (YPD) media (Solario, Beijing, China).…”