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1.
Nat Med ; 25(6): 1001-1011, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142850

RESUMO

The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.


Assuntos
Microbiota , Gravidez/fisiologia , Vagina/microbiologia , Adulto , Afro-Americanos , Biodiversidade , Estudos de Coortes , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Microbiota/genética , Microbiota/fisiologia , Classe Social
2.
Nat Med ; 25(6): 1012-1021, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142849

RESUMO

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.


Assuntos
Microbiota , Nascimento Prematuro/microbiologia , Vagina/microbiologia , Adulto , Afro-Americanos , Biodiversidade , Estudos de Coortes , Citocinas/metabolismo , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Recém-Nascido , Mediadores da Inflamação/metabolismo , Estudos Longitudinais , Metagenômica , Microbiota/genética , Microbiota/imunologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/imunologia , Fatores de Risco , Estados Unidos , Vagina/imunologia , Adulto Jovem
3.
Infect Immun ; 81(9): 3442-50, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23836816

RESUMO

The transferrin-binding proteins TbpA and TbpB enable Neisseria gonorrhoeae to obtain iron from human transferrin. The lipoprotein TbpB facilitates, but is not strictly required for, TbpA-mediated iron acquisition. The goal of the current study was to determine the contribution of two conserved regions within TbpB to the function of this protein. Using site-directed mutagenesis, the first mutation we constructed replaced the lipobox (LSAC) of TbpB with a signal I peptidase cleavage site (LAAA), while the second mutation deleted a conserved stretch of glycine residues immediately downstream of the lipobox. We then evaluated the resulting mutants for effects on TbpB expression, surface exposure, and transferrin iron utilization. Western blot analysis and palmitate labeling indicated that the lipobox, but not the glycine-rich motif, is required for lipidation of TbpB and tethering to the outer membrane. TbpB was released into the supernatant by the mutant that produces TbpB LSAC. Neither mutation disrupted the transport of TbpB across the bacterial cell envelope. When these mutant TbpB proteins were produced in a strain expressing a form of TbpA that requires TbpB for iron acquisition, growth on transferrin was either abrogated or dramatically diminished. We conclude that surface tethering of TbpB is required for optimal performance of the transferrin iron acquisition system, while the presence of the polyglycine stretch near the amino terminus of TbpB contributes significantly to transferrin iron transport function. Overall, these results provide important insights into the functional roles of two conserved motifs of TbpB, enhancing our understanding of this critical iron uptake system.


Assuntos
Sequência Conservada , Ferro/metabolismo , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/metabolismo , Proteína B de Ligação a Transferrina/genética , Proteína B de Ligação a Transferrina/metabolismo , Transferrina/metabolismo , Motivos de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Transporte de Íons , Mutagênese Sítio-Dirigida/métodos , Mutação/genética , Peptídeos/metabolismo , Transporte Proteico/genética
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