A mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium

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Autor(es): dc.contributorFederal University of Saõ Carlos-
Autor(es): dc.contributorUniversity of Saõ Paulo-
Autor(es): dc.contributorHarvard Medical School-
Autor(es): dc.contributorMassachusetts Eye and Ear Infirmary-
Autor(es): dc.contributorFaculdade de Medicina de Saõ José Do Rio Preto-FAMERP-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversity of Pittsburgh School of Medicine-
Autor(es): dc.creatorMello, Suelen S.-
Autor(es): dc.creatorVan Tyne, Daria-
Autor(es): dc.creatorLebreton, Francois-
Autor(es): dc.creatorSilva, Simone Q. [UNESP]-
Autor(es): dc.creatorNogueira, Mara C. L.-
Autor(es): dc.creatorGilmore, Michael S.-
Autor(es): dc.creatorCamargo, Ilana L. B. C.-
Data de aceite: dc.date.accessioned2022-02-22T00:32:34Z-
Data de disponibilização: dc.date.available2022-02-22T00:32:34Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1093/jac/dkz403-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/201092-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/201092-
Descrição: dc.descriptionObjectives: To verify dissemination of daptomycin-non-susceptible Enterococcus faecium in a hospital where daptomycin was not in use and to understand the evolutionary pathways connecting daptomycin hypersusceptibility to non-susceptibility. Methods: Clonality of 26 E. faecium was assessed by PFGE and the STs of these isolates were determined. The most daptomycin-susceptible isolate was evolved in vitro by stepwise daptomycin selection, generating isolates for genome comparisons. Results: The spread of a high-risk daptomycin-non-susceptible VRE clone was detected, as was the occurrence of an unusual daptomycin-hypersusceptible strain (HBSJRP18). To determine the basis for daptomycin hypersusceptibility, we evolved HBSJRP18 in vitro and identified candidate genetic alterations potentially related to daptomycin susceptibility. Both lafB, encoding glycosyltransferase, which is putatively involved in lipoteichoic acid (LTA) biosynthesis, and dak, encoding a dihydroxyacetone kinase likely involved in fatty acid metabolism, were mutated in multiple independent experiments. Trans-complementation showed that the lafB polymorphism naturally occurring in HBSJRP18 caused its daptomycin hypersusceptibility. Fourier-transform infrared spectroscopy identified differences between the extracted LTA spectra from the hypersusceptible isolate and its revertant, as well as other non-susceptible variants, supporting a role for LafB in E. faecium LTA biosynthesis. Zeta potential difference was detected in one evolved dak mutant derivative. While much more susceptible to daptomycin, HBSJRP18 showed enhanced growth in the presence of piperacillin, suggesting that this, or another cell wall-targeting antibiotic, may have selected for the daptomycin-hypersusceptible phenotype. Conclusions: Our findings provide new information on the basis for daptomycin susceptibility in E. faecium, with implications for limiting the development and spread of daptomycin resistance.-
Descrição: dc.descriptionFederal University of Saõ Carlos-
Descrição: dc.descriptionSaõ Carlos Institute of Physics University of Saõ Paulo-
Descrição: dc.descriptionHarvard Medical School-
Descrição: dc.descriptionMassachusetts Eye and Ear Infirmary-
Descrição: dc.descriptionDepartamento de Doenca¸s Dermatológicas Infecciosas e Parasitárias Faculdade de Medicina de Saõ José Do Rio Preto-FAMERP-
Descrição: dc.descriptionInstituto de Biociências Letras e Ciências Exatas (IBILCE) UNESP-
Descrição: dc.descriptionDepartments of Ophthalmology Microbiology and Immunobiology Harvard Medical School-
Descrição: dc.descriptionDivision of Infectious Diseases University of Pittsburgh School of Medicine, 3550 Terrace Street-
Descrição: dc.descriptionInstituto de Biociências Letras e Ciências Exatas (IBILCE) UNESP-
Formato: dc.format36-45-
Idioma: dc.languageen-
Relação: dc.relationJournal of Antimicrobial Chemotherapy-
???dc.source???: dc.sourceScopus-
Título: dc.titleA mutation in the glycosyltransferase gene lafB causes daptomycin hypersusceptibility in Enterococcus faecium-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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