Banca de QUALIFICAÇÃO: JESSICA KAROLINE DE LIMA SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JESSICA KAROLINE DE LIMA SILVA
DATE: 22/10/2025
TIME: 14:00
LOCAL: Virtual GOOGLE MEET meet.google.com/bcs-ithi-dsi
TITLE:

Microevolution of antifungal resistance in Candida (Candidozyma) auris select by exposure to fungicide

KEY WORDS:

tebuconazole; fluconazole; agrochemicals; cross-resistance; one health.

PAGES: 72
BIG AREA: Ciências Biológicas
AREA: Microbiologia
SUMMARY:

Candida (Candidozyma) auris is an emerging pathogenic yeast frequently associated with hospital outbreaks. Certain clades within the species exhibit high rates of antifungal resistance and multidrug resistance, with fluconazole (FCZ) resistance being the most prevalent, reaching up to 77% of isolates. One of the main challenges regarding C. auris is understanding how its resistance mechanisms have evolved. One hypothesis is that the extensive use of agricultural azoles in the environment may select resistant isolates that subsequently infect humans. In this context, the present study aimed to investigate whether exposure to the agricultural azole tebuconazole (TBZ) could select for cross-resistance to FCZ, while also evaluating the role of temperature in this adaptive process. Initially, susceptibility tests to FCZ and TBZ were performed on thirty-nine isolates of C. auris, according to CLSI (2017) guidelines. The results revealed 41% resistance to FCZ, while 38.5% of isolates exhibited reduced susceptibility to TBZ. Notably, 94% (15/16) of FCZ-resistant isolates also displayed elevated MIC values for TBZ, indicating cross-resistance in 38.5% of cases. All isolates with reduced TBZ susceptibility were resistant to FCZ, reinforcing the hypothesis that environmental azole use may contribute to the emergence of clinical resistance. To further investigate this relationship, adaptation experiments were conducted with three isolates susceptible to FCZ and TBZ, originating from different geographic regions. The isolates were serially exposed, in duplicate, to fixed concentrations of TBZ (16× MIC) under two temperature conditions (30 °C and 37 °C). This serial exposure led to a progressive increase in MIC values for TBZ and, more prominently, for FCZ, particularly at 37ºC, suggesting that thermal stress enhances the selection of resistant phenotypes. The stability of this phenotype was evaluated by subsequent passages in drug-free medium, revealing transient cross-resistance in all isolates. Additionally, adaptation experiments with increasing TBZ concentrations (up to 256 μg/mL) showed that some colony groups acquired permanent cross-resistance even after drug withdrawal. Taken together, these findings demonstrate that exposure to TBZ can induce resistance to FCZ in C. auris, particularly under thermal stress, highlighting the role of the environment in the selection and maintenance of resistant isolates of clinical importance.

COMMITTEE MEMBERS:
Presidente - 1143204 - RAFAEL WESLEY BASTOS
Externa à Instituição - DÉBORA CASTELO BRANCO DE SOUZA COLLARES MAIA
Externa à Instituição - LYSANGELA RONALTE ALVES - FIOCRUZ