The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

Abstract

This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains.

Antifungal Resistance Regarding Malassezia pachydermatis: Where Are We Now?

“…Based on different in vitro tests, some studies have reported high resistance rates for various agents [21][22][23][24]. According to some authors, the appearance of resistant strains would be a concern [25], while a low azole susceptibility of the yeast would be a well-documented phenomenon [26]. Instead, other studies have reported a substantial efficacy against yeastby the antifungal agents of more common use in dogs [27][28][29].…”

Genomic Tandem Quadruplication is Associated with Ketoconazole Resistance in Malassezia pachydermatis

“…Most M. pachydermatis strains are susceptible to ketoconazole; however, the occurrence of resistant strains has been reported [11,12]. To date, only one study has investigated the mechanisms of azole resistance in M. pachydermatis [13]. The study suggested an involvement of drug efflux pumps [13]; however, it used drug efflux pump inhibitors, not a molecular genetic approach.…”

“…To date, only one study has investigated the mechanisms of azole resistance in M. pachydermatis [13]. The study suggested an involvement of drug efflux pumps [13]; however, it used drug efflux pump inhibitors, not a molecular genetic approach.…”

Dermatitis Facial por Malassezia pachydermatis.

“…También existen terapias alternativas coadyuvantes para el tratamiento como es el uso de Oxitiamina para el tratamiento superficial de las micosis, especialmente las causadas por la especie M. pachydermatis, ya que demostró ser particularmente sensible. [12,13,22] Identificar específicamente el agente causal de las diferentes infecciones micóticas nos permite conocer mejor su epidemiología, distribución geográfica y patogenia, así como también la elección de los antifúngicos para un tratamiento adecuado. [1,2,9,10,11,13,14,15,16,17].…”