Úloha ABC transportéru v lékové rezistenci Acanthamoeba castellanii.

Drncová, Eliška

The ABC transporter protein family holds one of the key roles in drug resistance of a plethora of human pathogens. The ABC transporters partake in cellular efflux of various substrates, like drugs. Their function, also known as multi drug resistance (MDR), complicates the treatment of many diseases including pathogens from every domain of life. A unicellular human parasite Acanthamoeba castellanii, the cause of acanthamoeba keratitis and granulomatous acanthamoeba encephalitis, eludes most treatments, which results in a poor prognosis. Arecently identified ABC transporter was found to partake in the response to oxidative stress, induced by PEITC and rotenone in A. castellanii. Herein, its presumed role in drug resistance was investigated utilizing molecular techniques to characterise the functional properties of this ABC transporter. The response of the ABC transporter to PEITC, rotenone and amphotericin B was observed in a transcription analysis. Subsequently. a partial knockout strain was produced, and showed a promising phenotype in PEITC, suggesting the involvement of the ABC transporter in PEITC detoxification. Furthermore, based on the acquired data we propose, that more substrate specific ABC transporters are involved in the drug resistance of A. castellanii. However, the knockout method was proven...

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