Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers.
Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence-associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease.


OBJECTIVE
Group B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we compared the genomic profile of GBS samples causing infections in newborns with that of the GBS colonizing their mothers. Multiple mutations were detected, namely, within key virulence factors, including the response regulator CovR and surface protein Rib, potentially affecting the pathogenesis of GBS. Their overall impact was supported by differences in the expression of virulence-associated genes in human blood. Our results suggest that during GBS's progression to disease, particular variants are positively selected, contributing to the ability of this bacterium to infect its host.
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Paris, France CNRS UMR3525, Paris, France Université Pierre et Marie Curie, Paris, France.
Alexandre
A
Almeida
Institut Pasteur, Plateforme de Bio-Analyse Génomique, Paris, France.
Adrien
A
Villain
Service de Bactériologie, Centre National de Référence des Streptocoques, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Assistance Publique Hôpitaux de Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France INSERM, U1016, Paris, France CNRS (UMR 8104), Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Caroline
C
Joubrel
Service de Bactériologie, Centre National de Référence des Streptocoques, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Assistance Publique Hôpitaux de Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France.
Gérald
G
Touak
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Paris, France CNRS UMR3525, Paris, France.
Elisabeth
E
Sauvage
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Paris, France CNRS UMR3525, Paris, France.
Isabelle
I
Rosinski-Chupin
Service de Bactériologie, Centre National de Référence des Streptocoques, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, Assistance Publique Hôpitaux de Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France INSERM, U1016, Paris, France CNRS (UMR 8104), Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France claire.poyart@cch.aphp.fr pglaser@pasteur.fr.
Claire
C
Poyart
Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Paris, France CNRS UMR3525, Paris, France Institut Pasteur, Plateforme de Bio-Analyse Génomique, Paris, France claire.poyart@cch.aphp.fr pglaser@pasteur.fr.
Philippe
P
Glaser
D000328:Adult; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology*; D013290:Streptococcal Infections / Q000382:microbiology* / Q000635:transmission; D013292:Streptococcus agalactiae / Q000235:genetics*