Revealing the impact of Rapamycin on the virulence factors of the Candida haemulonii complex

• Published in: Current research in microbial sciences 2024-01, Vol.7, p.100247, Article 100247
• Main Authors: Alves, Vinicius, de Andrade, Iara Bastos, Corrêa-Junior, Dario, Avellar-Moura, Igor, Passos, Karini, Soares, Juliana, Pontes, Bruno, Almeida, Marcos Abreu, Almeida-Paes, Rodrigo, Frases, Susana
• Format: Article
• Language: English
• Subjects: Antifungal resistance; Candida haemulonii complex; from the special issue: Past, Present and Future of Antifungals: Advancements in Mechanisms of Action and Resistance, edited by André Santos, Maryam Roudbary, Célia Fortuna Rodrigues and Marta Branquinha; Rapamycin
• ISSN: 2666-5174; 2666-5174
• DOI: 10.1016/j.crmicr.2024.100247

•Invasive caNdida infections rising, impacting immunocompromised individuals.•Limited tools for C. haemulonii complex hinder clinical data availability.•C. haemulonii exhibits resistance to multiple antifungals, requiring new approaches.•Rapamycin impacts various virulence factors in C. haemulonii. The incidence of invasive fungal infections caused by Candida species is increasing, particularly in immunocompromised individuals. This increasing incidence poses a dual challenge, comprising escalating antifungal resistance and the necessity for accurate fungal identification. The Candida haemulonii complex further complicates these challenges due to limited identification tools. Like some other Candida species, infections involving this complex show resistance to multiple antifungals, requiring innovative therapeutic approaches. Rapamycin, known for its antifungal properties and immunosuppressive characteristics, was investigated against the C. haemulonii complex species. Results revealed a rapamycin minimal inhibitory concentration (MIC) range of 0.07 to >20 µM, with fungicidal effects in most strains. In vitro analyses using the rapamycin maximum plasma concentration (0.016 µM) showed reduced surface properties and decreased production of extracellular enzymes. Rapamycin also hindered biofilm formation by some strains. Even when treated at the human therapeutic dose, which is lower than the MIC, phenotypic variations in C. haemulonii were detected, hinting at the possible attenuation of some virulence factors when exposed to rapamycin. [Display omitted]