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PreprintCited by 40Neonatal and Maternal InfectionsGestational Diabetes Research and ManagementReproductive tract infections research

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Gestational diabetes augments group B Streptococcu s perinatal infection through disruptions in maternal immunity and the vaginal microbiota

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Mercado-Evans, Vicki, Mejia, Marlyd E., Zulk, Jacob J., Ottinger, Samantha, Hameed, Zainab, Serchejian, Camille, Marunde, Madelynn G., Robertson, Clare M., Ballard, Mallory B., Korotkova, Natalia, Flores, Anthony R., Pennington, Kathleen A., Patras, Kathryn A.·2023·Nature Communications
DOI 10.1101/2023.06.23.546252PMC PMC10838280

Preprint — published as 10.1038/s41467-024-45336-6 · Paper page

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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. We interrogated host-pathogen dynamics in a novel murine GDM model of GBS colonization and perinatal transmission. GDM mice had greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing revealed differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase ( yfhO ), and altered host responses. GDM disruption of immunity included reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered vaginal cytokines. Lastly, we observed distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Our translational model of GBS perinatal transmission in GDM hosts recapitulates several clinical aspects and enables discovery of host and bacterial drivers of GBS perinatal disease.

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Metadata

Authors
Mercado-Evans, V., Mejia, M. E., Zulk, J. J., Ottinger, S., Hameed, Z., Serchejian, C., Marunde, M. G., Robertson, C. M., Ballard, M. B., Korotkova, N., Flores, A. R., Pennington, K. A., & Patras, K. A.
Affiliations
  • Baylor College of Medicine (US)
  • University of Kentucky (US)
  • Memorial Hermann (US)
Corresponding author
Patras, Kathryn A.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-06-23
Volume
15
Issue
1
Pages
1035-1035
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.06.23.546252
PMC
PMC10838280
OpenAlex
W4391509793
Cited by
40
References
2
Citations by year
2026: 15 · 2025: 19 · 2024: 5 · 2023: 1
FWCI
16.09
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health and Human Services (AI157981, AI173448, DK128053)
  • Burroughs Wellcome Fund (NGP10103)
  • Cancer Prevention and Research Institute of Texas (CPRIT-RP180672, RP210227, RP180672, CA125123, RR024574)
  • Infectious Diseases Society of America
  • National Institutes of Health (CPRIT-RP180672, NIH T32, CA125123 and RR024574, DK056338, CA125123)
  • National Cancer Institute (CA125123, RR024574, P30CA125123)
  • National Institute of General Medical Sciences (T32GM152777, R25GM056929, T32GM136554)
  • National Institute of Allergy and Infectious Diseases (AI157981, R21AI173448, R21AI149366, F31AI167538, F31AI167547, U19AI157981)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK128053, P30DK056338, R01DK128053)
  • National Center for Research Resources (S10RR024574)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (AI173448, F31HD111236)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and Maternal Infections
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
Keywords
gestational diabetes mellitus, Streptococcus agalactiae, perinatal transmission, maternal immunity, vaginal microbiota, natural killer cells, placenta, neonatal diseases, bacterial adaptation to host, dysbiosis
MeSH terms
Animals, Female, Humans, Pregnancy, Streptococcal Infections, Streptococcus, Streptococcus agalactiae, Vagina, Cytokines, Diabetes, Gestational, Infectious Disease Transmission, Vertical, Mice, Microbiota

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