Proteomics

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Proteome of candida glabrata after Caspofungin exposure


ABSTRACT: Caspofungin resistance is a great concern, as the echinocandin drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, some pathways which regulate cellular stress responses could be crucial for enabling the evolution and maintenance of drug resistance. In this work, the first objective was to identify resistant mechanisms by whole genome sequencing in echinocandin-resistant C. glabrata. Then, studies of the proteomic response to caspofungin exposure and the analysis of the impact of calcineurin inhibitors on susceptibility, stress tolerance, biofilm formation, and pathogenicity in Galleria mellonella were conducted. The caspofungin resistant isolate only presented mutation in the FKS gene. Based on proteomic results, we identified 21 proteins whose abundance changed in response to caspofungin exposure. Some of these proteins are involved in wall biosynthesis, pathogenesis, and response to stress. Also, we showed that antifungal drugs in combination with CaM/Cal inhibitors could be an excellent therapeutic option, proved in an in-vitro and in-vivo model. Results, that could be potentially used to improve the outcomes of fungal diseases, especially now that antifungal resistance is increasing.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Candida Glabrata (yeast) (torulopsis Glabrata)

TISSUE(S): Blood

SUBMITTER: Concha Gil  

LAB HEAD: Concha Gil

PROVIDER: PXD021578 | Pride | 2022-04-04

REPOSITORIES: Pride

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Publications

Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistant Candida glabrata.

Ceballos-Garzon Andres A   Ceballos-Garzon Andres A   Monteoliva Lucia L   Gil Concha C   Alvarez-Moreno Carlos C   Vega-Vela Nelson E NE   Engelthaler David M DM   Bowers Jolene J   Le Pape Patrice P   Parra-Giraldo Claudia M CM  

The Journal of antimicrobial chemotherapy 20220201 3


<h4>Background</h4>Echinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets.<h4>Objectives</h4>We determi  ...[more]

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