Figure 1.

Drug-resistance mechanisms employed by amastigotes of Leishmania spp. (A) Deletion or reduced expression of drug transporters such as aquaglyceroporin 1 (AQP1) can diminish cellular drug uptake. (B) The overexpression of ABC transporters like MDR1, ABCI4, ABCG4 or ABCG6 helps the parasite efflux the drug and diminish its effect [25]. (C) Target alteration involves (i) the modification of the target to reduce drug binding, (ii) the substitution of the target by a new protein with a similar function that is not inhibited by the drug, (iii) the association of a target protection protein with the target, and iv) target overproduction to compensate for the drug’s inhibitory effect [26,27]. (D) Drug inactivation can occur through modification, hydrolysis, or the sequestration of the drug, rendering it ineffective [25,26]. (E) Drug exocytosis involves the encapsulation and expulsion of the drug or its conjugates from the parasite cell, usually thorough the flagellar pocket [25]. These mechanisms collectively enable the parasite to evade the therapeutic effects of drugs and persist in the host.