Metabolomic and Proteomic Changes in Candida albicans Biofilm in Response to Zosteric Acid Treatment

Abstract

Zosteric acid (ZA) is a secondary metabolite of the seagrass Zostera marina, with antibiofilm activity against fungi. Information concerning its mechanisms of action is lacking and this limits the development of more potent derivatives based on the same target and activity structure. The aim of this work was to investigate the ZA mode of action by analyzing the metabolic status of Candida albicans biofilm and its protein expression profile upon ZA treatment. Fourier-Transform Infrared Spectroscopy confirmed that ZA modified the metabolomic response of treated cells, showing changes in the spectral regions, mainly related to the protein compartment. Nano Liquid Chromatography–High-Resolution Mass Spectrometry highlighted that 10 proteins were differentially expressed in the C. albicans proteome upon ZA treatment. Proteins involved in the biogenesis, structure and integrity of cell walls as well as adhesion and stable attachment of hyphae were found downregulated, whereas some proteins involved in the stress response were found overexpressed. Additionally, ZA was involved in the modulation of non-DNA-based epigenetic regulatory mechanisms triggered by reactive oxygen species. These results partially clarified the ZA mechanism of action against fungi and provided insight into the major C. albicans pathways responsible for biofilm formation.

Multi-Omics Profiling of Candida albicans Grown on Solid Versus Liquid Media

“…The proteome of C. albicans has been extensively described elsewhere [40][41][42][43][44]. To our knowledge, there have not been any direct comparisons made between the proteome or metabolome of C. albicans (or other pathogenic fungi) in liquid cell culture versus solid media.…”

“…Recently, multi-omics analysis has made a major contribution to the field of medical microbiology [35][36][37][38], specifically liquid chromatography-mass spectrometry-based, and proteomics/metabolomics approaches have provided the research community with key molecular and cellular elements that provide a comprehensive understanding of microbial system biology and important aspects of microbial physiology [35,36,39]. Of note, until now, most of the multi-omics studies performed on C. albicans were performed in liquid media, which has been, beyond any doubt, a valuable contribution to this research field (e.g., [40][41][42][43][44]). However, there are well-known limitations in performing proteomics/metabolomics analysis in liquid medium.…”

Candida albicans: Pathogenesis and Secretory Pathways

“…The oligosaccharide of Dol-PP-GlcNAc 2 Man 5 is produced by a combination of the sugar of mannose (Man) and N-acetyl-D-glucosamine (GlcNAc). In this biosynthetic pathway, GDP-Man and UDP-GlcNAc act as donor substrates or sugar donors [48][49][50].…”

Unlocking the Antibiofilm Potential of Natural Compounds by Targeting the NADH:quinone Oxidoreductase WrbA

“…This and other experimental evidence have led to the assessment that chronic sub-lethal oxidative conditions promote the sessile behavior in A. vinelandii [ 14 ]. On the other hand, the natural compound zosteric acid (ZA) was found to hinder biofilm development at non-lethal concentrations [ 15 , 16 , 17 ] leading to the accumulation of ROS and the activation of scavenging mechanisms in both bacterial and fungal biofilm model systems [ 18 , 19 ]. The imminent oxidative stress was supposed to act as a cue, prompting bacteria to activate effective scavenging mechanisms or to shift metabolic pathways [ 20 ].…”