Candida tropicalisAntifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

ABSTRACTCandida tropicalisranks between third and fourth among Candidaspecies most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalisis usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalisresistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalisstrains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitrocorrelated very well with the results obtained in vivousing the model host Galleria mellonella. Using this panel of strains, the G. mellonellamodel system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivocorrelation of antifungals in C. tropicalis. The development in C. tropicalisof antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies.