Mecanismos Moleculares de Resistência Medicamentosa em Leishmania e suas Implicações para a Terapêutica
DOI:
https://doi.org/10.55892/jrg.v8i19.2573Palavras-chave:
Leishmaniose, Resistência a Fármacos, Mecanismos Moleculares, Medicina de PrecisãoResumo
A leishmaniose é uma zoonose vetorial causada por protozoários do gênero Leishmania cujo tratamento representa um desafio global. A terapia atual baseia-se num arsenal farmacológico limitado e tóxico, incluindo antimoniais pentavalentes, anfotericina B e miltefosina, e sua eficácia é cada vez mais comprometida pelo surgimento de resistência. Esta revisão integrativa sintetiza as evidências recentes sobre os complexos mecanismos moleculares de resistência do parasita. Entre os principais estão mutações em transportadores de membrana (como a aquagliceroporina AQP1), amplificações gênicas (a exemplo do gene MRPA) e alterações na biossíntese de esteróis, que diminuem a suscetibilidade aos fármacos. Adicionalmente, a acentuada plasticidade genômica de Leishmania, manifestada por seletiva dos medicamentos. Diante deste cenário, propõe-se um framework de medicina de precisão que integra diagnóstico molecular para diferenciar aneuploidias e reprogramação translacional, permite uma rápida adaptação à pressão resistência genética de tolerância fenotípica, vigilância epidemiológica regionalizada e o uso de terapias combinadas. O objetivo final é fornecer subsídios para decisões clínicas personalizadas, reduzir a disseminação de cepas resistentes e orientar o desenvolvimento de novos fármacos, incluindo aqueles ativos contra formas quiescentes do parasita, visando a erradicação completa e a sustentabilidade do tratamento.
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