Gestational Diabetes Augments Group B Streptococcus Infection by Disrupting Maternal Immunity and the Vaginal Microbiota

Authors

Vicki Mercado-Evans
Marlyd E Mejia
Jacob J Zulk
Samantha Ottinger
Zainab A Hameed
Camille Serchejian
Madelynn G Marunde
Clare M Robertson
Mallory B Ballard
Simone H Ruano
Natalia Korotkova
Anthony R Flores
Kathleen A Pennington
Kathryn A Patras

Publication Date

2-3-2024

Journal

Nature Communications

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.

Keywords

Pregnancy, Female, Humans, Animals, Mice, Diabetes, Gestational, Infectious Disease Transmission, Vertical, Microbiota, Cytokines, Vagina, Streptococcus, Streptococcus agalactiae, Streptococcal Infections

Comments

Supplementary Materials

PMID: 38310089