Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections.
Group B Streptococcus (GBS) is a common commensal bacterium in adults, but is also the leading cause of invasive bacterial infections in neonates in developed countries. The β-hemolysin/cytolysin (β-h/c), which is always associated with the production of an orange-to-red pigment, is a major virulence factor that is also used for GBS diagnosis. A collection of 1,776 independent clinical GBS strains isolated in France between 2006 and 2013 was evaluated on specific medium for β-h/c activity and pigment production. The genomic sequences of nonhemolytic and nonpigmented (NH/NP) strains were analyzed to identify the molecular basis of this phenotype. Gene deletions or complementations were carried out to confirm the genotype-phenotype association. Sixty-three GBS strains (3.5%) were NH/NP, and 47 of these (74.6%) originated from invasive infections, including bacteremia and meningitis, in neonates or adults. The mutations are localized predominantly in the cyl operon, encoding the β-h/c pigment biosynthetic pathway and, in the abx1 gene, encoding a CovSR regulator partner. In conclusion, although usually associated with GBS virulence, β-h/c pigment production is not absolutely required to cause human invasive infections. Caution should therefore be taken in the use of hemolysis and pigmentation as criteria for GBS diagnosis in routine clinical laboratory settings.
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France.
Anne
A
Six
Institut Pasteur, Unité Biologie des Bactéries Pathogènes à Gram Positif, Paris, France CNRS ERL3526, Paris, France.
Arnaud
A
Firon
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France Centre National de Référence des Streptocoques, Paris, France.
Céline
C
Plainvert
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France.
Camille
C
Caplain
Abdelouhab
A
Bouaboud
Centre National de Référence des Streptocoques, Paris, France.
Gérald
G
Touak
Centre National de Référence des Streptocoques, Paris, France.
Nicolas
N
Dmytruk
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France.
Magalie
M
Longo
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France.
Franck
F
Letourneur
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France Centre National de Référence des Streptocoques, Paris, France.
Agnès
A
Fouet
Institut Pasteur, Unité Biologie des Bactéries Pathogènes à Gram Positif, Paris, France CNRS ERL3526, Paris, France.
Patrick
P
Trieu-Cuot
INSERM U 1016, Institut Cochin, Team Barriers and Pathogens, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris, Paris, France DHU Risques et Grossesse, Assistance Publique Hôpitaux de Paris, Paris, France Institut Pasteur, Unité Biologie des Bactéries Pathogènes à Gram Positif, Paris, France CNRS ERL3526, Paris, France Centre National de Référence des Streptocoques, Paris, France Hôpitaux Universitaires Paris Centre Cochin-Hôtel Dieu-Broca, Assistance Publique Hôpitaux de Paris, Paris, France claire.poyart@aphp.fr.
Claire
C
Poyart
D000328:Adult; D001431:Bacteriological Techniques; D003470:Culture Media / Q000737:chemistry; D005602:France / Q000453:epidemiology; D017353:Gene Deletion; D056726:Genetic Association Studies; D005816:Genetic Complementation Test; D016680:Genome, Bacterial; D006460:Hemolysin Proteins / Q000032:analysis*; D006801:Humans; D007231:Infant, Newborn; D010860:Pigments, Biological / Q000032:analysis*; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*
D003470:Culture Media; D006460:Hemolysin Proteins; D010860:Pigments, Biological