Pesquisa identifica alterações genéticas que causam resistência a medicamentos contra a tuberculose
Pesquisadores de cinco instituições, entre elas a Fiocruz Minas, estão envolvidos em um projeto que vai contribuir para superar um dos principais obstáculos no combate à tuberculose: a resistência a medicamentos usados no tratamento da doença. Desenvolvida por um número cada vez maior de pacientes, a resistência acontece quando as bactérias causadoras da infecção sofrem mutações genéticas, fazendo com que os antibióticos aplicados se tornem ineficazes. Por isso, os cientistas que estão à frente do projeto pretendem, por meio da bioinformática, obter uma compreensão aprofundada a respeito dessas alterações, identificando quais delas interferem no efeito dos medicamentos e que tipo de reações provocam no organismo do paciente, de forma a apontar tratamentos mais personalizados.
“Hoje, um dos principais problemas no enfrentamento da tuberculose resistente é o intervalo de tempo entre a suspeita e a confirmação de que o medicamento não está fazendo efeito. Assim, um dos nossos principais objetivos é agilizar esse diagnóstico, identificando o mais rápido possível as mutações responsáveis pela resistência, para que o tratamento possa ser reavaliado e modificado, tendo em vista as características da bactéria que está causando a doença”, explica o pesquisador da Fiocruz Minas Douglas Pires.
Para identificar e caracterizar as mutações, os pesquisadores Douglas Pires e David Ascher, da University of Melbourne (Austrália), desenvolverem um método computacional, o MCSM, primeira plataforma online capaz de predizer o efeito das alterações genéticas. Por meio dela, é possível analisar as estruturas moleculares de proteínas que sejam alvo das drogas e que tenham sofrido mutações, a partir de amostras de pacientes que tiveram resistência a medicamentos. A ferramenta, cujo principal diferencial é a capacidade de lidar com grande quantidade de dados, também realiza cálculos matemáticos, permitindo prever novas mutações, antes que aconteçam.
A plataforma vem sendo alimentada por um banco de dados proveniente do Bloomsbury Research Institute, na Inglaterra. São mais 3500 amostras de pacientes de diversas regiões do mundo, incluindo o Brasil, que desenvolveram resistência a medicamentos contra a tuberculose.
“Em Bloomsburry, a profa. Sharon Peacock vem realizando um trabalho de longa data que consiste em catalogar e fazer o sequenciamento do genoma de amostras de paciente com tuberculose. É de lá que recebemos as cepas a serem analisadas”, explica Pires.
O estudo se completa com o envio das análises computacionais para Universidade de São Paulo (USP) e para a University of Cambridge, no Reino Unido, onde dois outros grupos envolvidos no projeto ficam responsáveis pela validação do estudo, por meio de ensaios biofísicos. “Ou seja, é o resultado computacional voltando para a clínica, para que sejam propostos melhores tratamentos e identificadas novos alvos para o desenvolvimento de fármacos”, destaca Pires.
A pesquisa vai ao encontro da recomendação da Organização Mundial de Saúde (OMS) que, no início deste mês, emitiu uma declaração enfatizando a necessidade de estudos e desenvolvimento de novos medicamentos para enfrentar a tuberculose multidroga resistente. A OMS estima que, em 2015, tenha sido registradas 250 mil mortes relacionadas a essa questão.
Matéria publicada originalmente no Especial Tuberculose, da Agência Fiocruz de Notícias.
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