Francisco Italo Rodrigues Gomes¹, Pedro Filho Noronha de Souza¹, Nicholas Silva dos Santos Filho¹, João Lucas Timbó Mororó¹, Felipe Pantoja Mesquita¹, Raquel Carvalho Montenegro¹

Candida albicans is one of the main pathogenic species in humans, responsible for opportunistic infections, particularly in immunocompromised individuals. Its resistance to multiple classes of antifungal agents, especially azoles, polyenes, and echinocandins, contributes to high mortality rates and poses a significant therapeutic challenge. Therefore, the development of new antifungal strategies is crucial. In this context, synthetic antimicrobial peptides have emerged as promising alternatives, as they have a low probability of inducing antimicrobial resistance. This study investigated  the mechanisms of action of the synthetic peptide PepGAT, bioinspired by the chitinase from Arabidopsis thaliana, against C. albicans. Proteomic analysis revealed changes in the proteomic profile of C. albicans cells treated with PepGAT, affecting several key pathways involved in cell development and drug resistance. Additionally, enzymatic activity assays showed that PepGAT decreased the activity of the enzyme superoxide dismutase (SOD) while increasing catalase (CAT) activity, suggesting an impact on the cellular redox system. An ergosterol interaction assay was performed, in which PepGAT-treated cells exhibited a loss of activity, indicating a possible interaction between PepGAT and exogenous ergosterol. Furthermore, fluorescence microscopy revealed an increase in cell membrane permeability, evidenced by the formation of pores of at least 6 kDa. These findings indicate that PepGAT exhibits multiple mechanisms of action against C. albicans, highlighting its potential as an alternative antifungal.

Agradecimentos: À Universidade Federal do Ceará, pela infraestrutura disponibilizada, e à CAPES, pelo apoio financeiro.