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Novos inibidores da biossíntese do peptidoglicano no tratamento da tuberculose
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A tuberculose (TB) é uma doença com longos séculos de existência originada pela infeção pela bactéria Mycobacterium tuberculosis (Mtb), descoberta por Robert Koch em 1882. Esta doença é responsável por uma grande morbilidade e mortalidade, sendo mesmo classificada pela OMS como uma das 10 doenças mais mortais a nível mundial. Ainda que, ao longo dos anos, se tenha vindo a verificar um pequeno decréscimo na taxa de incidência da doença, o número de infetados continua a ser elevado, estando longe o fim desta epidemia.
A utilização dos primeiros fármacos no tratamento da tuberculose, em 1944, revelou-se muito positiva, tendo-se conseguido a cura de determinados doentes. No entanto, rapidamente o bacilo de Koch desenvolveu mecanismos que o tornaram resistente a estes medicamentos. O aparecimento de estirpes resistentes, multirresistentes e extensamente resistentes agravou ainda mais este problema de Saúde Pública, pois são estirpes mais difíceis de tratar e requerem terapêuticas mais prolongadas.
Mtb tornou-se resistente a todos os fármacos introduzidos até à data contra a tuberculose, pelo que o predomínio das estirpes com diferentes níveis de resistência na população e a maior mortalidade associada a estas têm vindo a tornar-se um grave problema de Saúde Pública, longe de estar controlado. Assim, é necessário que se estimule o interesse na descoberta de novas moléculas capazes de combater as estirpes resistentes, devendo ser acompanhado da implementação de medidas que permitam aumentar a eficácia do tratamento da doença.
O peptidoglicano (PG), um dos principais constituintes da parede celular das bactérias, é essencial para a integridade e sobrevivência bacteriana. O estudo da sua via biossintética e a caracterização das enzimas que participam na sua síntese, essenciais para a bactéria, fornece novos alvos moleculares para os quais podem ser desenvolvidos compostos que permitam a sua inibição. Apesar de estarem já descritas moléculas que são inibidoras das enzimas de biossíntese do PG a sua eficácia em Mtb é limitada devido à escassez da investigação nesta bactéria. No entanto, essa investigação é essencial para que se possa controlar a epidemia e erradicar a doença a nível mundial, um dos objetivos da Agenda Sustentável da ONU, até 2030.
Tuberculosis is a disease that has been around for centuries and it is caused by the bacteria Mycobacterium tuberculosis (Mtb) discovered by Robert Koch in 1882. Having high morbidity and mortality rates, this disease is classified by the WHO (World Health Organization) as one of the deadliest diseases worldwide. Although the incidence rate has been reducing over the years, the number of infected individuals is still very high which means that the end of this epidemic is still nowhere in sight. The first drugs used against tuberculosis in 1944, were a tremendous success by even allowing the cure of some patients. However, Koch’s bacillus rapidly developed mechanisms that made them resistant to these drugs. The emergence of resistant, multi-resistant and extensively resistant strains exacerbated this serious public health issue since strains that are harder to treat require more prolonged therapeutics. Mtb became resistant to all drugs introduced against it so far, and thus the growing incidence of strains with varied levels of resistance in the population, as well as the higher mortality associated with those has become a serious and uncontrolled public health issue. Therefore, stimulating the interest in the discovery of new molecules able to fight the resistant strains in addition to implementing measures that increase the efficiency of the treatment is of utmost importance. Peptidoglycan, one of the main components of the bacterial cell wall, is essential for the bacterial integrity and survival. The study of its biosynthetic pathway and characterization of the enzymes that participate in it can provide numerous molecular targets that could be inhibited by possible compounds. Although enzyme inhibitors have already been discovered, their efficiency in Mtb is limited due to the lack of research on these bacteria. Hence this research is crucial to control this epidemic and reach the 2030 UNO goal of eradicating this disease from the world.
Tuberculosis is a disease that has been around for centuries and it is caused by the bacteria Mycobacterium tuberculosis (Mtb) discovered by Robert Koch in 1882. Having high morbidity and mortality rates, this disease is classified by the WHO (World Health Organization) as one of the deadliest diseases worldwide. Although the incidence rate has been reducing over the years, the number of infected individuals is still very high which means that the end of this epidemic is still nowhere in sight. The first drugs used against tuberculosis in 1944, were a tremendous success by even allowing the cure of some patients. However, Koch’s bacillus rapidly developed mechanisms that made them resistant to these drugs. The emergence of resistant, multi-resistant and extensively resistant strains exacerbated this serious public health issue since strains that are harder to treat require more prolonged therapeutics. Mtb became resistant to all drugs introduced against it so far, and thus the growing incidence of strains with varied levels of resistance in the population, as well as the higher mortality associated with those has become a serious and uncontrolled public health issue. Therefore, stimulating the interest in the discovery of new molecules able to fight the resistant strains in addition to implementing measures that increase the efficiency of the treatment is of utmost importance. Peptidoglycan, one of the main components of the bacterial cell wall, is essential for the bacterial integrity and survival. The study of its biosynthetic pathway and characterization of the enzymes that participate in it can provide numerous molecular targets that could be inhibited by possible compounds. Although enzyme inhibitors have already been discovered, their efficiency in Mtb is limited due to the lack of research on these bacteria. Hence this research is crucial to control this epidemic and reach the 2030 UNO goal of eradicating this disease from the world.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Tuberculose Parede celular Peptidoglicano Resistência a antibióticos Inibidores enzimáticos Mestrado integrado - 2021