Perinatal hormones favor CC17 group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates.

Constantin Hays,Asmaa Tazi,Abdelouhab Bouaboud,Agnès Fouet,Gérald Touak,Claire Poyart,Julie Guignot

doi:10.7554/elife.48772

Abstract

Group B Streptococcus (GBS) is the leading cause of invasive bacterial neonatal infections. Late-onset diseases (LOD) occur between 7 and 89 days of life and are largely due to the CC17 GBS hypervirulent clone. We studied the impact of estradiol (E2) and progesterone (P4), which impregnate the fetus during pregnancy, on GBS neonatal infection in cellular and mouse models of hormonal exposure corresponding to concentrations found at birth (E2-P4 C0) and over 7 days old (E2-P4 C7). Using representative GBS isolates, we show that E2-P4 C7 concentrations specifically favor CC17 GBS meningitis following mice oral infection. CC17 GBS crosses the intestinal barrier through M cells. This process mediated by the CC17-specific surface protein Srr2 is enhanced by E2-P4 C7 concentrations which promote M cell differentiation and CC17 GBS invasiveness. Our findings provide an explanation for CC17 GBS responsibility in LOD in link with neonatal gastrointestinal tract maturation and hormonal imprint.

Highlights

Group B Streptococcus (Streptococcus agalactiae, GBS) is a natural inhabitant of the gastrointestinal and vaginal flora of 10% to 30% healthy individuals
Using an approach combining murine and cellular models of infection with one CC17 and one non-CC17 representative GBS isolates, both of capsular serotype III and responsible for neonatal disease, we demonstrate that hormonal exposure to E2 and P4 concentrations found in 7-day-old neonates (E2-P4 C7) favors CC17 GBS pathogeny in comparison to E2 and P4 levels found at birth (E2-P4 C0)
We used a murine model of meningitis following oral gavage and intestinal translocation to determine whether hormonal concentrations could impact GBS and more CC17 GBS infection

Summary

Introduction

Group B Streptococcus (Streptococcus agalactiae, GBS) is a natural inhabitant of the gastrointestinal and vaginal flora of 10% to 30% healthy individuals. CC17 GBS expresses specific surface proteins which promote intestinal colonization and confer blood brain barrier (BBB) translocation abilities in animal models (Six et al, 2015; Tazi et al, 2010) This clone is less responsible for EOD and largely underrepresented in GBS adult diseases (Huber et al, 2011; Martins et al, 2012) implying that specific host factors might be involved in CC17 GBS invasiveness in >7 day-old neonates. One particular aspect of the perinatal life is the very high concentration of pregnancy-related hormones, especially estradiol (E2) and progesterone (P4), to which neonates are exposed all along pregnancy This hormonal exposure leads to neonatal circulating concentrations at birth which are more than 500 times superior to those of a male adult (Lagiou et al, 2014). The increased invasiveness of CC17 GBS in E2-P4 C7 condition is linked to an enhanced crossing of the intestinal barrier through M cells which is mediated by the CC17-specific surface protein Srr

Results

Discussion

Materials and methods

Histological procedures and staining

Funding Funder