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Avaliação de compostos com potencial antimicrobiano em espécies de bactérias multirresistentes
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Orientador(es)
Resumo(s)
Os antibióticos estão entre as mais importantes classes de fármacos alguma vez descobertas na
história da medicina, permitindo o tratamento de infeções bacterianas, mas também a execução
de outros atos médico-cirúrgicos. No entanto, o seu uso excessivo e desregulado tem levado a um
aumento do surgimento de bactérias resistentes aos mesmos, ao qual se associa a falta de inovação
de moléculas com ação antibacteriana e o desinvestimento da indústria farmacêutica nesta área.
Como consequência, a resistência bacteriana é atualmente considerada uma das principais
ameaças à saúde pública global. Neste contexto, em 2017, a Organização Mundial de Saúde
publicou uma lista onde constavam as espécies de bactérias que representavam uma maior ameaça
à saúde pública, a qual fora recentemente atualizada em Maio de 2024. Em ambas as versões da
lista, figuram as espécies Acinetobacter baumannii, Klebsiella pneumoniae e Pseudomonas
aeruginosa, as quais são responsáveis por cerca de 40% das infeções nosocomiais, estando
associadas a um maior nível de mortalidade e morbilidade, tendo ainda impactos na economia
dos sistemas de saúde. Os níveis de resistência destas três espécies de bactérias estão a atingir
níveis alarmantes na atualidade, não existindo compostos antimicrobianos inovadores eficazes
contra estas. Neste sentido, o presente estudo teve como objetivo contribuir para a descoberta de
novos compostos antimicrobianos promissores para estas três espécies, através da execução de
um screening fenotípico de uma coleção de 577 compostos químicos em estirpes bacterianas de
A. baumannii, K. pneumoniae e P. aeruginosa. Os resultados permitiram a identificação de 13
compostos com atividade contra as estirpes de A. baumannii, 2 contra K. pneumoniae e apenas 1
contra P. aeruginosa. Esperamos que os compostos aqui identificados possam servir como ponto
de partida para estudos futuros e, possivelmente, para produção de novos medicamentos
antibacterianos.
Antibiotics are one the most important types of drugs in the history of medicine, allowing the treatment of bacterial infections, but also the execution of other medical therapies. However, nowadays there is an uncontrolled use of these drugs, and consequently the available antibiotics are becoming useless, and the rising of resistant bacteria is increasing. Simultaneously, there is a lack of innovation in terms of the discovery of new molecules with antimicrobial activity and a disinvestment of the pharmaceutical industry in this area as well. As a result, bacterial resistance is considered one of the biggest threatens to the public health nowadays. In this way, in 2017 the World Health Organization published a list, recently updated in May 2024, with the most problematic bacteria species to the public health. Accordingly with the both versions of this list, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa are three of the most problematic species of resistant bacteria nowadays. These three bacterial species are responsible for approximately 40% of nosocomial infections, contributing for patients’ mortality and morbidity, and affecting the health system economy. The conventional pharmacological treatments to fight these bacteria are becoming powerless and, in this sense, the research for new therapeutic alternatives is necessary and urgent, particularly the discovery and development of new potential antimicrobial molecules. In this way, the main goal of this study is to do a phenotypic screening of 577 chemical compounds in bacterial strains of these three species, in order to identify potential antimicrobial compounds. The results allowed to identify 13 compounds with antimicrobial activity against A. baumannii, 2 against K. pneumoniae and only 1 against P. aeruginosa. With this work, we hope to contribute for the identification of new lead compounds with potential antimicrobial activity, that in the future could be used as medicines.
Antibiotics are one the most important types of drugs in the history of medicine, allowing the treatment of bacterial infections, but also the execution of other medical therapies. However, nowadays there is an uncontrolled use of these drugs, and consequently the available antibiotics are becoming useless, and the rising of resistant bacteria is increasing. Simultaneously, there is a lack of innovation in terms of the discovery of new molecules with antimicrobial activity and a disinvestment of the pharmaceutical industry in this area as well. As a result, bacterial resistance is considered one of the biggest threatens to the public health nowadays. In this way, in 2017 the World Health Organization published a list, recently updated in May 2024, with the most problematic bacteria species to the public health. Accordingly with the both versions of this list, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa are three of the most problematic species of resistant bacteria nowadays. These three bacterial species are responsible for approximately 40% of nosocomial infections, contributing for patients’ mortality and morbidity, and affecting the health system economy. The conventional pharmacological treatments to fight these bacteria are becoming powerless and, in this sense, the research for new therapeutic alternatives is necessary and urgent, particularly the discovery and development of new potential antimicrobial molecules. In this way, the main goal of this study is to do a phenotypic screening of 577 chemical compounds in bacterial strains of these three species, in order to identify potential antimicrobial compounds. The results allowed to identify 13 compounds with antimicrobial activity against A. baumannii, 2 against K. pneumoniae and only 1 against P. aeruginosa. With this work, we hope to contribute for the identification of new lead compounds with potential antimicrobial activity, that in the future could be used as medicines.
Descrição
Tese de Mestrado, Biologia Molecular e Genética, 2024, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Resistência Antimicrobiana Screening Fenotípico Compostos Antimicrobianos Patógenos ESKAPE Bactérias Gram-negativas Teses de mestrado - 2024