Unmasking the Amphotericin B Resistance Mechanisms in Candida haemulonii Species Complex

• DOI: 10.1021/acsinfecdis.0c00117
• Publication Date: 2020-04-02T17:35:13Z
• Authors: Laura N. Silva; Simone S. C. Oliv...; Lucas B. Magalhães; Valter V. Andrade...; Eduardo C. Torres...; Mariana D. C. Car...; Marcos D. Pereira; Marta H. Branquinha; André L. S. Santos
• Keywords: Ergosterol; Mitochondrial respiratory chain; Efflux; Membrane permeability; Polyene

The polyene amphotericin B (AMB) exerts a powerful and broad antifungal activity. AMB acts by (i) binding to ergosterol, leading pore formation at the fungal plasma membrane with subsequent ion leakage, (ii) inducing intracellular accumulation of reactive oxygen species (ROS). Herein, we have deciphered resistance mechanisms in clinical isolates Candida haemulonii complex (C. haemulonii, C. duobushaemulonii, var. vulnera) comparison other clinically relevant non-albicans species. Membrane gas chromatography–mass spectrometry analysis revealed that vast majority sterols were composed ergosterol pathway intermediates, evidencing absence target. Supporting this data, demonstrated poor permeability after treatment. Regarding oxidative burst, induced ROS all tested; however, phenomenon was slightly seen isolates. Our results indicated these displayed altered respiratory status, as their growth nonfermented carbon sources, low consumption oxygen, derisive mitochondrial potential. use specific inhibitors chain (complex I–IV) no effects on yeast growth, highlighting metabolic shift fermentative strains. Also, proved be highly resistant burst agents, which can correlated high activity antioxidant enzymes. data primary evidence suggesting content, function, redox homeostasis are involved fungicidal might explain presented multidrug-resistant, emergent, opportunistic complex.