Bruno Souza Bonifácio¹, Ricardo Ferreira Lima¹, Mario Izidoro², Sérgio Schenkmam¹

Antimicrobial resistance (AMR) has long been considered one of the main threats to humans in the twenty-first century. An example of rapid and unstoppable Darwinian adaptation through natural selection is underway, in which microorganisms are constantly evolving to survive antimicrobials. In this fight, microorganisms have advantages unless effective approaches are developed to control and prevent the spread of AMR. Metabolomics, an emerging field within systems biology, aims at the comprehensive analysis of the set of metabolites present in an organism, offering a crucial window into understanding the biochemical changes that occur in response to various conditions, such as bacterial infections. This approach allows for the detailed study of metabolic reactions that are directly linked to the phenotypic expression of cells and their response to external stimuli, such as the presence of resistant bacteria and fungi. Metabolomics identifies characteristic metabolic profiles that reveal pathophysiological states and allows for a personalized medicine approach, targeting specific therapies. This project aims to provide new tools to accelerate the detection of AMR, which can be useful for diagnosis-based decisions, fitting into the main objectives of the ARIES project. Currently, two strains: Candida tropicalis ATCC 750 (wild-type) and C. tropicalis 1534/2017 (fluconazole-resistant) have been used in the first non-targeted metabolomic analyses, performed by gas chromatography and mass spectrometry. We identified a total of 78 metabolites. We saw that wild and resistant samples are metabolically different, both in the absence and presence of the antifungal. We highlight the metabolite eburicol, precursor of the de novo synthesis of ergosterol, as an important metabolite in the resistant strain. We may be the first target for a biomarker of resistant C. tropicalis. New analyses will be carried out to identify new targets. In addition, we have already started analyses of new strains of Candida parapsilosis, and soon analyses of Candida auris and albicans will also be made.

Agradecimentos: We would like to thank FAPESP for providing financial support to CEPID ARIES (Process: 2021/10599-3) and to our project (Process: 2024/18733-9; and Process: 2024/03612-1).