QseC inhibitors as an antivirulence approach for gram-negative pathogens

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUT Southwestern Medical Center-
Autor(es): dc.contributorOmm Scientific-
Autor(es): dc.contributorUniversity of Maryland School of Medicine-
Autor(es): dc.contributorUniversity of Toledo-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorCurtis, Meredith M.-
Autor(es): dc.creatorRussell, Regan-
Autor(es): dc.creatorMoreira, Cristiano G.-
Autor(es): dc.creatorAdebesin, Adeniyi M.-
Autor(es): dc.creatorWang, Changguang-
Autor(es): dc.creatorWilliams, Noelle S.-
Autor(es): dc.creatorTaussig, Ron-
Autor(es): dc.creatorStewart, Don-
Autor(es): dc.creatorZimmern, Philippe-
Autor(es): dc.creatorLu, Biao-
Autor(es): dc.creatorPrasad, Ravi N.-
Autor(es): dc.creatorZhu, Chen-
Autor(es): dc.creatorRasko, David A.-
Autor(es): dc.creatorHuntley, Jason F.-
Autor(es): dc.creatorFalck, John R.-
Autor(es): dc.creatorSperandio, Vanessa-
Data de aceite: dc.date.accessioned2025-08-21T16:46:42Z-
Data de disponibilização: dc.date.available2025-08-21T16:46:42Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2014-10-17-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1128/mBio.02165-14-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/227910-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/227910-
Descrição: dc.descriptionInvasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED 209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections.-
Descrição: dc.descriptionNational Institutes of Health-
Descrição: dc.descriptionDepartment of Microbiology UT Southwestern Medical Center-
Descrição: dc.descriptionDepartment of Biochemistry UT Southwestern Medical Center-
Descrição: dc.descriptionDepartment of Pharmacology UT Southwestern Medical Center-
Descrição: dc.descriptionOmm Scientific-
Descrição: dc.descriptionDepartment of Urology UT Southwestern Medical Center-
Descrição: dc.descriptionDepartment of Microbiology and Immunology and the Institute for Genome Sciences University of Maryland School of Medicine-
Descrição: dc.descriptionCollege of Medicine and Life Sciences University of Toledo-
Descrição: dc.descriptionBiological Sciences Department School of Pharmaceutical Sciences São Paulo State University-UNESPAraraquara-
Descrição: dc.descriptionBiological Sciences Department School of Pharmaceutical Sciences São Paulo State University-UNESPAraraquara-
Descrição: dc.descriptionNational Institutes of Health: 5 T32 AI7520-14-
Descrição: dc.descriptionNational Institutes of Health: AI053067-
Descrição: dc.descriptionNational Institutes of Health: AI077853-
Idioma: dc.languageen-
Relação: dc.relationmBio-
???dc.source???: dc.sourceScopus-
Título: dc.titleQseC inhibitors as an antivirulence approach for gram-negative pathogens-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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