Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Mol Microbiol ; 120(2): 258-275, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37357823

RESUMEN

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intraspecies diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low interspecies and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Furthermore, we observe subtype-specific effects of GBS T7SS on host colonization, as CJB111 subtype I but not CNCTC 10/84 subtype III T7SS promotes GBS vaginal colonization. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.


Asunto(s)
Infecciones Estreptocócicas , Sistemas de Secreción Tipo VII , Recién Nacido , Femenino , Humanos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sistemas de Secreción Tipo VII/genética , Virulencia , Operón/genética , Genitales Femeninos/metabolismo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/genética , Streptococcus agalactiae/metabolismo , Vagina/metabolismo , Vagina/microbiología
2.
Infect Immun ; 91(4): e0044022, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-36975791

RESUMEN

Group B Streptococcus (GBS) is a pervasive neonatal pathogen accounting for a combined half a million deaths and stillbirths annually. The most common source of fetal or neonatal GBS exposure is the maternal microbiota. GBS asymptomatically colonizes the gastrointestinal and vaginal mucosa of 1 in 5 individuals globally, although its precise role in these niches is not well understood. To prevent vertical transmission, broad-spectrum antibiotics are administered to GBS-positive mothers during labor in many countries. Although antibiotics have significantly reduced GBS early-onset neonatal disease, there are several unintended consequences, including an altered neonatal microbiota and increased risk for other microbial infections. Additionally, the incidence of late-onset GBS neonatal disease remains unaffected and has sparked an emerging hypothesis that GBS-microbe interactions in developing neonatal gut microbiota may be directly involved in this disease process. This review summarizes our current understanding of GBS interactions with other resident microbes at the mucosal surface from multiple angles, including clinical association studies, agriculture and aquaculture observations, and experimental animal model systems. We also include a comprehensive review of in vitro findings of GBS interactions with other bacterial and fungal microbes, both commensal and pathogenic, along with newly established animal models of GBS vaginal colonization and in utero or neonatal infection. Finally, we provide a perspective on emerging areas of research and current strategies to design microbe-targeting prebiotic or probiotic therapeutic intervention strategies to prevent GBS disease in vulnerable populations.


Asunto(s)
Enfermedades del Recién Nacido , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Femenino , Animales , Recién Nacido , Humanos , Embarazo , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae , Antibacterianos , Red Social , Complicaciones Infecciosas del Embarazo/microbiología
3.
Curr Opin Microbiol ; 77: 102422, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38215548

RESUMEN

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized microbiota murine models, used to define and mechanistically explore host-microbe interactions at the vaginal mucosa.


Asunto(s)
Medicina Clínica , Microbiota , Embarazo , Femenino , Humanos , Animales , Ratones , Metagenoma , Interacciones Microbiota-Huesped , Vagina
4.
Nat Commun ; 15(1): 1035, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310089

RESUMEN

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered maternofetal cytokines. Lastly, we observe distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Here, we show a model of GBS dissemination in GDM hosts that recapitulates several clinical aspects and identifies multiple host and bacterial drivers of GBS perinatal disease.


Asunto(s)
Diabetes Gestacional , Microbiota , Infecciones Estreptocócicas , Embarazo , Femenino , Humanos , Animales , Ratones , Transmisión Vertical de Enfermedad Infecciosa , Citocinas , Vagina/microbiología , Streptococcus , Streptococcus agalactiae , Infecciones Estreptocócicas/microbiología
5.
bioRxiv ; 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36747681

RESUMEN

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intra-species diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low inter-species and inter-subtype homology but contain similar domains/motifs and therefore may serve similar functions. We further identify orphaned GBS WXG100 proteins. Functionally, we show that GBS T7SS subtype I and III strains secrete EsxA in vitro and that in subtype I strain CJB111, esxA1 appears to be differentially transcribed from the T7SS operon. Further, we observe subtype-specific effects of GBS T7SS on host colonization, as subtype I but not subtype III T7SS promotes GBS vaginal persistence. Finally, we observe that T7SS subtypes I and II are the predominant subtypes in clinical GBS isolates. This study highlights the potential impact of T7SS heterogeneity on host-GBS interactions.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA