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Estratégias moleculares para o desenvolvimento de novos antibióticos
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Advisor(s)
Abstract(s)
Cada vez mais surgem novas estirpes bacterianas multirresistentes, resistentes ao arse-nal de antibióticos disponíveis para as combater (Huemer et al., 2020), constituindo uma das maiores ameaças para a saúde pública da atualidade (Hess, 2021). É estimado que até 2050 o número de infeções provocadas por estirpes multirresistentes ultrapassará os 10 milhões mun-dialmente e que estas levarão a um aumento significativo de mortes, ultrapassando o número de mortes provocadas por cancro (The Review, 2014).
Diversos fatores podem contribuir para o desenvolvimento de resistências, como a uti-lização incorreta de antibióticos, o que inclui a utilização em excesso de antibióticos de largo espectro, a aquisição de resistências devido a transferência horizontal de genes específicos como também um processo evolutivo por parte das bactérias (Courvalin, 2016).
No lado da indústria, o pipeline para novos antibióticos encontra-se escasso por diver-sos motivos, como o elevadíssimo custo de pesquisa e desenvolvimento. A ausência de novos antibióticos deixa poucas opções para o combate contra o aparecimento destas estirpes (Lewis, 2015). Por este motivo é essencial o desenvolvimento de novos antibióticos como também desenvolver estratégias para a ideação de novos antibióticos que se alarguem para além dos convencionais utilizados até hoje.
Estas estratégias têm incluído a pesquisa de novos alvos terapêuticos (Lewis, 2015), a inibição dos mecanismos de resistência antibiótica microbiana (Wetzel et al., 2021), a adoção do conceito multi-target (Wetzel et al., 2021), a utilização de péptidos antimicrobianos (Bopa-rai & Sharma, 2019), o desenvolvimento de antibacterianos inorgânicos ou/e organometálicos (Hess, 2021) e a aplicação de bacteriófagos (Song & Chung, 2010).
New multidrug resistant bacterial strain s are emerging , resistant to the arsenal of able antibiotics used to treat them (Huemer et al .., 2020), this constitutes one of the greatest threats to public health (Hess, 2021). It’s estimated that by 2050 the number of infections caused by multidrug resistant strains will exceed 10 million worldwide , and these will result in a significant increase in death s, surpassing the number of death s caused by cancer (The view, 2014). Several factors can contribute to the development of antibiotic resistance, like the in- correct use of antibiotics which includes the excessive use of broad spectrum antibiotics, the acquisition of resistance due to the horizontal gene transfer as well as evolutionary process es by bacteria (Courvalin, 2016). On the industry side, the pipeline for new antibiotics is scarce for several reasons, such as the extremely high cost of research and development. The absence of new antibiotics leaves few options to combat the emergence of these drug resistant strains (Lewis, 2015). For this reason, it is essential to develop new antibiotics, as well as to develop strategies for the creation of new antibiotics that go beyond the conventional ones used currently These strategies include the search for new therapeutic targets (Lewis, 2015), the inhi- bition of microbial antibiotic resistance mechanisms (Wetzel et al .., 2021), the implementation of a multi target concept (Wetzel et al .., 2021), the use of antimicrobial peptides (Boparai & Sharma, 2019), the development of inorganic and/or organometallic antibacterials (Hess, 2021) and the application of bacteriophages (Song & Chung, 2010).
New multidrug resistant bacterial strain s are emerging , resistant to the arsenal of able antibiotics used to treat them (Huemer et al .., 2020), this constitutes one of the greatest threats to public health (Hess, 2021). It’s estimated that by 2050 the number of infections caused by multidrug resistant strains will exceed 10 million worldwide , and these will result in a significant increase in death s, surpassing the number of death s caused by cancer (The view, 2014). Several factors can contribute to the development of antibiotic resistance, like the in- correct use of antibiotics which includes the excessive use of broad spectrum antibiotics, the acquisition of resistance due to the horizontal gene transfer as well as evolutionary process es by bacteria (Courvalin, 2016). On the industry side, the pipeline for new antibiotics is scarce for several reasons, such as the extremely high cost of research and development. The absence of new antibiotics leaves few options to combat the emergence of these drug resistant strains (Lewis, 2015). For this reason, it is essential to develop new antibiotics, as well as to develop strategies for the creation of new antibiotics that go beyond the conventional ones used currently These strategies include the search for new therapeutic targets (Lewis, 2015), the inhi- bition of microbial antibiotic resistance mechanisms (Wetzel et al .., 2021), the implementation of a multi target concept (Wetzel et al .., 2021), the use of antimicrobial peptides (Boparai & Sharma, 2019), the development of inorganic and/or organometallic antibacterials (Hess, 2021) and the application of bacteriophages (Song & Chung, 2010).
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Novos antibióticos Resistências Alvos Antimicrobiano