RESUMO
OBJECTIVES: The aim of this study was to investigate the structure of a broad and sustained hospital outbreak of OXA-48-producing Klebsiella pneumoniae (KpO48) belonging to sequence type 405 (ST405). METHODS: Whole-genome sequencing and comparison of ten ST405 KpO48 isolates obtained from clinical samples in our hospital was performed. Using stringent criteria, 36 single nucleotide polymorphisms (SNPs) were detected (range 0-21 in pairwise comparisons), and allele-specific PCR was used to call the SNPs among a larger set of isolates. RESULTS: Several haplotypes were identified within the population. The haplotypes did not show a spatial structure, but a temporal evolution of sequential haplotype replacements was observed. CONCLUSIONS: The dispersed spatial distribution suggests a reservoir formed by a large pool of colonised patients, and the temporal replacement pattern suggests that the sustained outbreak was composed of several small outbreaks that appeared and rapidly dispersed to several units.
Assuntos
Proteínas de Bactérias/metabolismo , Infecção Hospitalar/microbiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Genoma Bacteriano , Genômica , Hospitais/estatística & dados numéricos , Humanos , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/enzimologia , Filogenia , Polimorfismo de Nucleotídeo Único , beta-Lactamases/genéticaRESUMO
Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for â¼ 1%-2% of CdLS-like phenotypes.
Assuntos
Proteínas de Ciclo Celular/genética , Proteoglicanas de Sulfatos de Condroitina/genética , Proteínas Cromossômicas não Histona/genética , Síndrome de Cornélia de Lange/diagnóstico , Síndrome de Cornélia de Lange/genética , Heterozigoto , Mutação , Fenótipo , Alelos , Estudos de Coortes , Análise Mutacional de DNA , Exoma , Fácies , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MasculinoRESUMO
Klebsiella pneumoniae KpO3210 is a OXA-48 carbapenemase-producing isolate obtained from a blood culture in the context of an outbreak in Hospital Universitario La Paz (Madrid, Spain) in 2010. It belongs to the major clone detected during the outbreak and is resistant to all beta-lactams and to several other antibiotics.
