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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Analysis of Volatile Molecules Present in the Secretome of the Fungal Pathogen Candida glabrata
Juan Ernesto López-Ramos1, Elihú Bautista2, Guadalupe Gutiérrez-Escobedo1
1IPICYT, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, Camino a la Presa San José, #2055, Col. Lomas 4ª Sección, San Luis Potosí CP 78216, San Luis Potosí, Mexico.
Abstract:
Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis are the four most common human fungal pathogens isolated that can cause superficial and invasive infections. It has been shown that specific metabolites present in the secretomes of these fungal pathogens are important for their virulence. C. glabrata is the second most common isolate world-wide and has an innate resistance to azoles, xenobiotics and oxidative stress that allows this fungal pathogen to evade the immune response and persist within the host. Here, we analyzed and compared the C. glabrata secretome with those of C. albicans, C. parapsilosis, C. tropicalis and the non-pathogenic yeast Saccharomyces cerevisiae. In C. glabrata, we identified a different number of metabolites depending on the growth media: 12 in synthetic complete media (SC), 27 in SC-glutamic acid and 23 in rich media (YPD). C. glabrata specific metabolites are 1-dodecene (0.09 ± 0.11%), 2,5-dimethylundecane (1.01 ± 0.19%), 3,7-dimethyldecane (0.14 ± 0.15%), and octadecane (0.4 ± 0.53%). The metabolites that are shared with C. albicans, C. glabrata, C. parapsilosis, C. tropicalis and S. cerevisiae are phenylethanol, which is synthesized from phenylalanine, and eicosane and nonanoic acid (identified as trimethylsilyl ester), which are synthesized from fatty acid metabolism. Phenylethanol is the most abundant metabolite in all fungi tested: 26.36 ± 17.42% (C. glabrata), 46.77 ± 15.58% (C. albicans), 49.76 ± 18.43% (C. tropicalis), 5.72 ± 0.66% (C. parapsilosis.) and 44.58 ± 27.91% (S. cerevisiae). The analysis of C. glabrata's secretome will allow us to further our understanding of the possible role these metabolites could play in its virulence.
Insights
This study compares the secretomes of pathogenic yeasts, revealing phenylethanol as a common, abundant metabolite. Understanding these fungal metabolites aids in studying virulence factors of Candida glabrata.
Area of Science:
- Mycology
- Medical Mycology
- Biochemistry
Background:
- The four most common human fungal pathogens are Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis.
- Secreted metabolites from these fungi are crucial for their virulence.
- Candida glabrata exhibits innate resistance to azoles, xenobiotics, and oxidative stress, aiding immune evasion and host persistence.
Purpose of the Study:
- To analyze and compare the secretome of Candida glabrata with other pathogenic Candida species and Saccharomyces cerevisiae.
- To identify specific and shared metabolites across these fungal species.
- To investigate the potential role of these metabolites in Candida glabrata virulence.
Main Methods:
- Comparative secretome analysis of Candida glabrata, Candida albicans, Candida parapsilosis, Candida tropicalis, and Saccharomyces cerevisiae.
- Metabolite identification using gas chromatography-mass spectrometry (GC-MS) with trimethylsilyl derivatization.
- Quantification of identified metabolites across different growth media (synthetic complete, SC-glutamic acid, YPD).
Main Results:
- Candida glabrata secretome composition varied with growth media, yielding 12-27 metabolites.
- Specific metabolites identified in Candida glabrata include 1-dodecene, 2,5-dimethylundecane, 3,7-dimethyldecane, and octadecane.
- Phenylethanol, eicosane, and nonanoic acid were identified as shared metabolites; phenylethanol was the most abundant across all tested fungi.
Conclusions:
- Phenylethanol, synthesized from phenylalanine, is a highly abundant shared metabolite in pathogenic and non-pathogenic yeasts.
- The distinct secretome profile of Candida glabrata, including specific hydrocarbons, warrants further investigation.
- Understanding the role of these metabolites in fungal secretomes can elucidate virulence mechanisms, particularly for drug-resistant species like Candida glabrata.

