Abstract
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.
| Original language | English |
|---|---|
| Journal | Nature Communications |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2024 |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
Funding
This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672), the NIH (CA125123 and RR024574) and the assistance of Joel M. Sederstrom, Padmini Narayanan and Claude Chew. The Center for Metagenomics and Microbiology Research for 16 S sequencing (CMMR) and the Texas Medical Center Digestive Diseases Center (DDC), with funding from the NIH (DK056338), were also important resources for this study. This work was also supported in part by Cancer Prevention & Research Institute of Texas Proteomics & Metabolomics Core Facility Support Award (RP210227) and NCI Cancer Center Support Grant (P30CA125123) to the Antibody-based Proteomics Core/Shared Resource. We thank Susan F. Venable from the DDC and Shixia Huang, Zhongcheng Shi, Yuan Yao and Michael Nguyen from the Antibody-based Proteomics Core/Shared Resource for their excellent technical assistant in performing the Luminex experiments, data preliminary analyses and QC, and project consultation. We are also thankful to Misu A. Sanson-Iglesias and Luis A. Vega for helpful suggestions and resources for dual-RNA sequencing experiments and Anaid Reyes from the CMMR for assistance with 16S sequencing. Additionally, BioRender.com (2023) was used to generate experimental schematics. This work was supported by an NIH T32 award T32GM136554 to M.E.M. and J.J.Z. and NIH F31 award AI167547 to V.M.E., NIH F31 award AI167538 to M.E.M. and NIH F31 award HD111236 to SO. V.M.E. was also supported by a scholarship from Baylor Research Advocates for Student Scientists (BRASS) and a Grant for Emerging Researchers/Clinicians Mentorship Program from the Infectious Diseases Society of America (IDSA). Studies were supported by an R21 AI149366 to N.K., and a Burroughs Wellcome Fund Next Gen Pregnancy Initiative (NGP10103), NIH R01 (DK128053), U19 (AI157981), and R21 (AI173448) to K.A.P. This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672), the NIH (CA125123 and RR024574) and the assistance of Joel M. Sederstrom, Padmini Narayanan and Claude Chew. The Center for Metagenomics and Microbiology Research for 16 S sequencing (CMMR) and the Texas Medical Center Digestive Diseases Center (DDC), with funding from the NIH (DK056338), were also important resources for this study. This work was also supported in part by Cancer Prevention & Research Institute of Texas Proteomics & Metabolomics Core Facility Support Award (RP210227) and NCI Cancer Center Support Grant (P30CA125123) to the Antibody-based Proteomics Core/Shared Resource. We thank Susan F. Venable from the DDC and Shixia Huang, Zhongcheng Shi, Yuan Yao and Michael Nguyen from the Antibody-based Proteomics Core/Shared Resource for their excellent technical assistant in performing the Luminex experiments, data preliminary analyses and QC, and project consultation. We are also thankful to Misu A. Sanson-Iglesias and Luis A. Vega for helpful suggestions and resources for dual-RNA sequencing experiments and Anaid Reyes from the CMMR for assistance with 16S sequencing. Additionally, BioRender.com (2023) was used to generate experimental schematics. This work was supported by an NIH T32 award T32GM136554 to M.E.M. and J.J.Z. and NIH F31 award AI167547 to V.M.E., NIH F31 award AI167538 to M.E.M. and NIH F31 award HD111236 to SO. V.M.E. was also supported by a scholarship from Baylor Research Advocates for Student Scientists (BRASS) and a Grant for Emerging Researchers/Clinicians Mentorship Program from the Infectious Diseases Society of America (IDSA). Studies were supported by an R21 AI149366 to N.K., and a Burroughs Wellcome Fund Next Gen Pregnancy Initiative (NGP10103), NIH R01 (DK128053), U19 (AI157981), and R21 (AI173448) to K.A.P.
| Funders | Funder number |
|---|---|
| Baylor Research Advocates for Student Scientists | |
| Burroughs Wellcome Fund Next Gen Pregnancy Initiative | AI157981, DK128053, AI173448, NGP10103 |
| Cancer Prevention & Research Institute of Texas Proteomics & Metabolomics Core | RP210227 |
| Shixia Huang | |
| Texas Medical Center Digestive Diseases Center | |
| National Institutes of Health (NIH) | RR024574 |
| National Institutes of Health (NIH) | |
| National Childhood Cancer Registry – National Cancer Institute | P30CA125123, AI167538, HD111236, T32GM136554, AI167547 |
| National Childhood Cancer Registry – National Cancer Institute | |
| Infectious Diseases Society of America | R21 AI149366 |
| Infectious Diseases Society of America | |
| Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine | |
| Drug Discovery Center, College of Pharmacy, Health Science Center, University of Tennessee | DK056338 |
| Drug Discovery Center, College of Pharmacy, Health Science Center, University of Tennessee |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy
