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Technologies for high-throughput identification of antibiotic mechanism of action

2021-05-12Artigo científico Acesso aberto
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dc.contributor.authorRibeiro Da Cunha, Bernardo
dc.contributor.authorZoio, Paulo
dc.contributor.authorFonseca, Luís P. P.
dc.contributor.authorCalado, Cecília
dc.date.accessioned2021-06-04T10:12:52Z
dc.date.available2021-06-04T10:12:52Z
dc.date.issued2021-05-12
dc.descriptionEste trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2017 do Instituto Politécnico de Lisboa. Código de referência IPL/2017/DrugsPlatf/ISEL
dc.descriptionEste trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2020 do Instituto Politécnico de Lisboa. Código de referência IPL/2020/NephroMD/ISEL
dc.description.abstractThere are two main strategies for antibiotic discovery: target-based and phenotypic screening. The latter has been much more successful in delivering first-in-class antibiotics, despite the major bottleneck of delayed Mechanism-of-Action (MOA) identification. Although finding new antimicrobial compounds is a very challenging task, identifying their MOA has proven equally challenging. MOA identification is important because it is a great facilitator of lead optimization and improves the chances of commercialization. Moreover, the ability to rapidly detect MOA could enable a shift from an activity-based discovery paradigm towards a mechanism-based approach. This would allow to probe the grey chemical matter, an underexplored source of structural novelty. In this study we review techniques with throughput suitable to screen large libraries and sufficient sensitivity to distinguish MOA. In particular, the techniques used in chemical genetics (e.g., based on overexpression and knockout/knockdown collections), promoter-reporter libraries, transcriptomics (e.g., using microarrays and RNA sequencing), proteomics (e.g., either gel-based or gel-free techniques), metabolomics (e.g., resourcing to nuclear magnetic resonance or mass spectrometry techniques), bacterial cytological profiling, and vibrational spectroscopy (e.g., Fourier-transform infrared or Raman scattering spectroscopy) were discussed. Ultimately, new and reinvigorated phenotypic assays bring renewed hope in the discovery of a new generation of antibiotics.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCUNHA, Bernardo Ribeiro da; [et al] – Technologies for high-throughput identification of antibiotic mechanism of action. Antibiotics. ISSN 2079-6382. Vol. 10, N.º 5 (2021), pp. 1-20pt_PT
dc.identifier.doi10.3390/antibiotics10050565pt_PT
dc.identifier.issn2079-6382
dc.identifier.urihttp://hdl.handle.net/10400.21/13416
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationProjeto financiado no âmbito do Concurso de Projetos de Investigação, Desenvolvimento, Inovação & Criação Artística (IDI&CA) financiados pelo Instituto Politécnico de Lisboa. IPL/2017/DrugsPlatf/ISELpt_PT
dc.relationProjeto financiado no âmbito do Concurso de Projetos de Investigação, Desenvolvimento, Inovação & Criação Artística (IDI&CA) financiados pelo Instituto Politécnico de Lisboa. IPL/2020/NephroMD/ISELpt_PT
dc.subjectAntibiotic discoverypt_PT
dc.subjectBacterial cytological profilingpt_PT
dc.subjectChemical geneticspt_PT
dc.subjectHigh-throughput screeningpt_PT
dc.subjectMechanism-of-Action (MOA)pt_PT
dc.subjectMetabolomicspt_PT
dc.subjectPhenotypic screeningpt_PT
dc.subjectProteomicspt_PT
dc.subjectTranscriptomicspt_PT
dc.subjectVibrational spectroscopypt_PT
dc.titleTechnologies for high-throughput identification of antibiotic mechanism of actionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/BIO/69242/2006
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIO%2F69242%2F2006/PT
oaire.citation.endPage20pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleAntibioticspt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameRibeiro da Cunha
person.familyNameP. Fonseca
person.familyNameCalado
person.givenNameBernardo
person.givenNameLuis
person.givenNameCecília
person.identifier130332
person.identifier.ciencia-idEA1E-4BEA-A01E
person.identifier.ciencia-id951D-DF38-3397
person.identifier.ciencia-id9418-E320-3177
person.identifier.orcid0000-0002-0303-9416
person.identifier.orcid0000-0001-8429-6977
person.identifier.orcid0000-0002-5264-9755
person.identifier.ridP-6154-2017
person.identifier.ridA-4228-2013
person.identifier.ridE-2102-2014
person.identifier.scopus-author-id57211629814
person.identifier.scopus-author-id55916288400
person.identifier.scopus-author-id6603163260
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication810fc4c7-6c05-44a0-81e5-6cfdb3c2088a
relation.isAuthorOfPublication5c533551-5113-4c0a-93f1-9c50cbd796bc
relation.isAuthorOfPublicatione8577257-c64c-4481-9b2b-940fedb360cc
relation.isAuthorOfPublication.latestForDiscovery5c533551-5113-4c0a-93f1-9c50cbd796bc
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ISEL - Eng. Quim. Biol. - Artigos