Gardnerella Revisited: Species Heterogeneity, Virulence Factors, Mucosal Immune Responses, and Contributions to Bacterial Vaginosis

Infection and Immunity, Год журнала: 2023, Номер 91(5)

Опубликована: Апрель 18, 2023

species are associated with bacterial vaginosis (BV) and have been investigated as etiological agents of the condition. Nonetheless, isolation this taxon from healthy individuals has raised important questions regarding its role. Recently, using advanced molecular approaches,

Язык: Английский

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Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 29, 2024

Abstract Modulation of the cervix by steroid hormones and commensal microbiome play a central role in health female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate human cervical epithelial-stromal interface with functional epithelial barrier production mucus biochemical hormone-responsive properties similar to living cervix. When Cervix Chips are populated optimal healthy versus dysbiotic microbial communities (dominated Lactobacillus crispatus Gardnerella vaginalis , respectively), significant differences tissue innate immune responses, function, cell viability, proteome, composition observed those seen vivo. Thus, Organ represent physiologically relevant vitro study physiology host-microbiome interactions, hence may be used as preclinical testbed for development therapeutic interventions enhance women’s health.

Язык: Английский

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ILC3s regulate the gut microbiota via host intestinal galactosylation to limit pathogen infection in mice

Nature Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Язык: Английский

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The role of sialidases in the pathogenesis of bacterial vaginosis and their use as a promising pharmacological target in bacterial vaginosis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Март 1, 2024

Bacterial vaginosis (BV) is an infection of the genital tract characterized by disturbance normally Lactobacilli- dominated vaginal flora due to overgrowth Gardnerella and other anaerobic bacteria. vaginalis , pathogen major BV, produces sialidases that cleave terminal sialic acid residues off human glycans. By desialylation, not only alter function acid-containing glycoconjugates but also play a vital role in attachment, colonization spread many pathogens. With known pathogenic effects, excellent performance sialidase-based diagnostic tests, promising therapeutic potentials sialidase inhibitors, could be used as biomarker BV. This review explores sources their dysbiosis, aims better understand participation pathogenesis BV value diagnosis treatment

Язык: Английский

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Prevotella are major contributors of sialidases in the human vaginal microbiome

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(36)

Опубликована: Авг. 26, 2024

Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and vaginosis (BV). These negative effects may arise from sialidase-mediated degradation of protective mucus layer cervicovaginal environment. Prior biochemical studies vaginal sialidases have focused solely on BV-associated organism Gardnerella vaginalis . Despite their implications for sexual reproductive health, other bacteria not been characterized. Here, we show that Prevotella species produce possess variable toward mucin substrates. The sequences genes presence are largely conserved across clades different geographies, hinting at importance globally. Finally, find transcripts, those encoding mucin-degrading timonensis , highly prevalent abundant human genomes transcriptomes. Together, our results identify as a critical source microbiome, improving understanding this detrimental activity.

Язык: Английский

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Prevotella timonensis degrades the vaginal epithelial glycocalyx through high fucosidase and sialidase activities

mBio, Год журнала: 2024, Номер 15(9)

Опубликована: Авг. 20, 2024

ABSTRACT Bacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract. BV characterized by replacement health-associated Lactobacillus species diverse anerobic bacteria, including well-known Gardnerella vaginalis. Prevotella timonensis, and bivia are anerobes that found in significant number patients, but their contributions to disease process remain be determined. Defining characteristics overgrowth adherence mucosal surface increased activity mucin-degrading enzymes such as sialidases vaginal secretions. We demonstrate P. not bivia, strongly adheres endocervical cells similar level G. vaginalis did elicit comparable proinflammatory epithelial response. The timonensis genome uniquely encodes large set mucus-degrading enzymes, four putative fucosidases two sialidases, PtNanH1 PtNanH2. Enzyme assays demonstrated fucosidase sialidase activities cell-bound secreted fractions were significantly higher than for other anerobes. In assays, efficiently removed fucose α2,3- α2,6-linked sialic acid moieties from glycocalyx. Recombinantly expressed NanH1 NanH2 cleaved α2,3 acids surface, removal could blocked using inhibitors. This study demonstrates has distinct virulence-related properties include initial adhesion high capacity mucin degradation at surface. Our results underline importance understanding role different bacteria BV. IMPORTANCE common affects proportion women associated with reduced fertility risk secondary infections. most BV-associated bacterium, may also play an important role. showed that, , adhered well epithelium, suggesting both first stage infection. Compared was unique removing protective sugars cover epithelium. These underscore roles initiation development

Язык: Английский

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Prevotella timonensisdegrades the vaginal epithelial glycocalyx through high fucosidase and sialidase activities

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 9, 2024

Abstract Bacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract (FRT). BV characterized by replacement health-associated Lactobacillus species diverse anaerobic bacteria, including well-known Gardnerella vaginalis . Prevotella timonensis and bivia are anaerobes that found in significant percentage patients, but their pathogenic properties yet to be determined. Defining characteristics overgrowth adherence mucosal surface increased activity mucin-degrading enzymes such as sialidases vaginal secretions. Here, we demonstrate P. not strongly adhered endocervical cells similar level G. did elicit comparable pro-inflammatory response. The genome uniquely encodes large set mucus-degrading 4 putative fucosidases 2 sialidases, PtNanH1 PtNanH2. Enzyme assays demonstrated fucosidase sialidase cell-bound secreted fractions was significantly higher than for other anaerobes. Infection revealed efficiently removed fucose α2,3- α2,6-linked sialic acid moieties from epithelial glycocalyx. Recombinantly expressed NanH1 NanH2 α2,3 acids removal could blocked using inhibitors. This study demonstrates P has distinct virulence include initial adhesion high capacity mucin degradation at surface. Our results underline importance understanding role different bacteria BV. Significance statement (Layman) common affects women associated with reduced fertility risk secondary infections. most BV-associated bacterium, may also play an important role. We showed that, , well epithelium, suggesting both first stage infection. Compared unique removing protective sugars cover epithelium. These underscore roles initiation development

Язык: Английский

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Prevotellaare major contributors of sialidases in the human vaginal microbiome

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 9, 2024

Abstract Elevated bacterial sialidase activity in the female genital tract is strongly associated with poor health outcomes including preterm birth and vaginosis. These negative effects may arise from sialidase-mediated degradation of protective mucus layer cervicovaginal environment. Prior biochemical studies vaginal sialidases have focused solely on vaginosis-associated organism Gardnerella vaginalis . Despite their implications for sexual reproductive health, other bacteria not been characterized. Here, we show that Prevotella species produce active possess variable toward mucin. are highly conserved across clades different geographies, hinting at importance globally. Finally, find sialidases, mucin-degrading enzymes timonensis , prevalent abundant human metagenomes metatranscriptomes, Together, our results identify as a critical source microbiome, improving understanding this detrimental activity. Significance Statement Sialidase microbiome increased vaginosis adverse outcomes. release sialic acid host-derived glycans environment, altering structures functions. However, limited to one genus, In work, characterize multiple genus We more microbial communities than sialidases. Our work highlights an underappreciated important both therapeutic development.

Язык: Английский

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Sialidases derived from Gardnerella vaginalis remodel the sperm glycocalyx and impair sperm function

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiome, affects approximately 29 percent women worldwide (up to 50% in some regions) and is associated with several adverse health outcomes including preterm birth increased incidence sexually transmitted infection (STI). BV-associated bacteria, such as Gardnerella vaginalis Prevotella timonensis, damage mucosa through activity sialidase enzymes that remodel epithelial glycocalyx degrade mucin glycoproteins. This creates an inflammatory environment which likely contributes outcomes. However, whether glycolytic also sperm during their transit reproductive tract has not yet been determined. Here, we show sialidase-mediated remodeling human increases susceptibility within female tract. In particular, report desialylated demonstrate complement lysis agglutination, well decreased cervical mucus. Our results mechanism by sialidases may affect survival function potentially contribute infertility. Significance statement Sperm surface glycans are crucial for immune processes We found derived from bacteria resulting aberrant mucus trapping, complement-mediated cytolysis sperm. These implicate potential Classification: Biological Sciences, Immunology Inflammation,

Язык: Английский

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Cervical function in pregnancy and disease: new insights from single-cell analysis

American Journal of Obstetrics and Gynecology, Год журнала: 2025, Номер 232(4), С. S81 - S94

Опубликована: Апрель 1, 2025

Язык: Английский

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