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1.
Org Lett ; 23(4): 1500-1503, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33533625

RESUMO

Oxazoles are rapidly assembled through a sequential deprotonation-condensation of Asmic, anisylsulfanylmethylisocyanide, with esters followed by sulfanyl-lithium exchange-trapping. Deprotonating Asmic affords a metalated isocyanide that efficiently traps esters to afford oxazoles bearing a versatile C-4 anisylsulfanyl substituent. Interchange of the anisylsulfanyl substituent is readily achieved through a first-in-class sulfur-lithium exchange-electrophilic trapping sequence whose versatility is illustrated in the three-step synthesis of the bioactive natural product streptochlorin.

2.
Nat Med ; 26(6): 941-951, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32514171

RESUMO

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.


Assuntos
Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/genética , Equipamentos e Provisões Hospitalares/microbiologia , Controle de Infecções , Microbiota/genética , Leitos/microbiologia , Biofilmes , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/transmissão , Desinfecção , Farmacorresistência Bacteriana Múltipla/genética , Contaminação de Equipamentos , Mapeamento Geográfico , Humanos , Metagenômica , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Infecções Oportunistas/transmissão , Quartos de Pacientes , Singapura , Análise Espaço-Temporal , Centros de Atenção Terciária
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