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

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.

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The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Journal of Experimental Medicine ◽

10.1084/jem.20092594 ◽

2010 ◽

Vol 207 (11) ◽

pp. 2313-2322 ◽

Cited By ~ 159

Author(s):

Asmaa Tazi ◽

Olivier Disson ◽

Samuel Bellais ◽

Abdelouhab Bouaboud ◽

Nicolas Dmytruk ◽

...

Keyword(s):

Epithelial Cells ◽

Late Onset ◽

Group B Streptococcus ◽

Intestinal Barrier ◽

Surface Protein ◽

Oral Route ◽

Neonatal Meningitis ◽

Promising Target ◽

Single Clone ◽

Group B

Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17–specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood–brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies.

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Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001–2018

BMC Infectious Diseases ◽

10.1186/s12879-020-05599-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Tina Perme ◽

Daniel Golparian ◽

Maja Bombek Ihan ◽

Andrej Rojnik ◽

Miha Lučovnik ◽

...

Keyword(s):

Pregnant Women ◽

Virulence Factors ◽

Late Onset ◽

Group B Streptococcus ◽

Genomic Diversity ◽

Neonatal Disease ◽

Phenotypic Characterisation ◽

High Prevalence ◽

Group B ◽

The Impact

Abstract Background Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. Methods GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. Results Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. Conclusions A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

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Group B Streptococcus (Streptococcus agalactiae)

10.1093/med/9780190604813.003.0019 ◽

2018 ◽

Author(s):

Kirsty Le Doare ◽

Christine E. Jones ◽

Paul T. Heath

Keyword(s):

Early Onset ◽

Late Onset ◽

Group B Streptococcus ◽

Significant Risk ◽

Neonatal Infection ◽

Significant Risk Factor ◽

Invasive Disease ◽

Neurodevelopmental Outcomes ◽

Intrapartum Antibiotic ◽

Group B

Group B Streptococcus (GBS) is a leading cause of early neonatal infection and neonatal mortality, with long-term adverse neurodevelopmental outcomes in up to 50% of survivors of GBS meningitis. GBS has a likely underappreciated role in causing preterm birth and stillbirth. GBS colonizes the vagina and gastrointestinal tract of the pregnant woman, and transmission to the infant occurs during or just before delivery. Although the majority of these infants do not develop invasive disease, maternal colonization is a prerequisite for early onset disease (0–6 days of life, most commonly associated with sepsis and respiratory distress) and a significant risk factor for late onset disease (7–89 days of life, most commonly associated with sepsis and meningitis). The introduction of intrapartum antibiotic prophylaxis has resulted in significant declines in the incidence of early onset disease but provides no protection against late onset disease.

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Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein

Infection and Immunity ◽

10.1128/iai.70.9.4897-4901.2002 ◽

2002 ◽

Vol 70 (9) ◽

pp. 4897-4901 ◽

Cited By ~ 42

Author(s):

Denis Martin ◽

Stéphane Rioux ◽

Edith Gagnon ◽

Martine Boyer ◽

Josée Hamel ◽

...

Keyword(s):

Protective Immunity ◽

Group B Streptococcus ◽

Surface Protein ◽

Neonatal Infection ◽

Active Immunization ◽

Infection Model ◽

Lethal Challenge ◽

Specific Antibodies ◽

Pregnant Mice ◽

Group B

ABSTRACT The protective potential of antibodies directed against group B streptococcus (GBS) Sip surface protein was determined by using the mouse neonatal infection model. Rabbit Sip-specific antibodies administered passively to pregnant mice protected their pups against a GBS lethal challenge. In addition, active immunization with purified recombinant Sip protein of female CD-1 mice induced the production of specific antibodies that also confer protection to the newborn pups against GBS strains of serotypes Ia/c, Ib, II, III, and V. These data confirm that Sip-specific antibodies can cross the placenta and conferred protective immunity against GBS infections.

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The impact of group B streptococcus prophylaxis on late-onset neonatal infections

Journal of Perinatology ◽

10.1038/jp.2012.76 ◽

2012 ◽

Vol 33 (3) ◽

pp. 206-211 ◽

Cited By ~ 10

Author(s):

K L Ecker ◽

P K Donohue ◽

K S Kim ◽

J A Shepard ◽

S W Aucott

Keyword(s):

Late Onset ◽

Group B Streptococcus ◽

Neonatal Infections ◽

Group B ◽

The Impact

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Streptococcus agalactiae colonization and screening approach in high-risk pregnant women in southern Brazil

The Journal of Infection in Developing Countries ◽

10.3855/jidc.12025 ◽

2020 ◽

Vol 14 (04) ◽

pp. 332-340

Author(s):

Jeane Zanini da Rocha ◽

Jéssica Feltraco ◽

Vanessa Radin ◽

Carla Vitola Gonçalves ◽

Pedro Eduardo Almeida da Silva ◽

...

Keyword(s):

High Risk ◽

Pregnant Women ◽

Low Cost ◽

Group B Streptococcus ◽

Neonatal Morbidity ◽

Neonatal Infection ◽

Diagnostic Methods ◽

Antenatal Screening ◽

Group B ◽

The Impact

Introduction: Considering that Group B Streptococcus (GBS) persists as an important cause of neonatal morbidity and mortality, the objective of this study was to evaluate the frequency of maternal colonization by GBS, comparing the culture by the Granada broth with the GeneXpert real-time PCR diagnostic methods and the impact of chemoprophylaxis in high-risk pregnant women. Methodology: A prospective cohort of 110 pregnant women hospitalized for gestational complications was formed and recruited following interview and collection of rectovaginal swabs. Results: The frequency of maternal colonization was 28.2% and statistically associated with Capurro> 37 weeks (p = 0.030) and neonatal infection (p = 0.008). Chemoprophylaxis was offered to 80% of those colonized. Among the pregnant women treated, a fivefold reduction in the rate of prematurity and rate of neonatal infection was observed. The sensitivity was 76.6% and 86.6% in culture and PCR, respectively, with an optimal index of agreement between the methods (K = 0.877). Grenade culture was considered an easy and low-cost method, while GeneXpert presented higher cost and error rate of 10%. However, 23.3% of the pregnant women were diagnosed exclusively by GeneXpert and the results were obtained in two hours. Conclusions: This study showed a significant prevalence of maternal colonization for GBS and that both culture and molecular methods had peculiarities that allow different applicability, with the culture being feasible for antenatal screening and in the hospital for high-risk pregnant women with no sign of imminent delivery and GeneXpert being prioritized for situations of preterm birth.

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Prevalence, Risk Factors, and Serotype Distribution of Group B Streptococcus Colonization in HIV-Infected Pregnant Women Living in Belgium: A Prospective Cohort Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy320 ◽

2018 ◽

Vol 5 (12) ◽

Cited By ~ 2

Author(s):

Nicolas Dauby ◽

Catherine Adler ◽

Veronique Y Miendje Deyi ◽

Rosalie Sacheli ◽

Laurent Busson ◽

...

Keyword(s):

Risk Factors ◽

Pregnant Women ◽

Late Onset ◽

Group B Streptococcus ◽

Neonatal Infection ◽

Colonization Rate ◽

Vaccine Serotypes ◽

Related Data ◽

Significant Difference ◽

Group B

Abstract Background Group B streptococcus (GBS) infection is a leading cause of severe neonatal infection. Maternal GBS carriage during pregnancy is the main risk factor for both early-onset and late-onset GBS disease. High incidence of GBS infection has been reported in HIV-exposed but -uninfected infants (HEU). We aimed to determine the prevalence, characteristics, and risk factors for GBS colonization in HIV-infected and HIV-uninfected pregnant women living in Belgium. Methods Between January 1, 2011, and December 31, 2013, HIV-infected (n = 125) and -uninfected (n = 120) pregnant women had recto-vaginal swabs at 35–37 weeks of gestation and at delivery for GBS detection. Demographic, obstetrical, and HIV infection–related data were prospectively collected. GBS capsular serotyping was performed on a limited number of samples (33 from HIV-infected and 16 from HIV-uninfected pregnant women). Results There was no significant difference in the GBS colonization rate between HIV-infected and -uninfected pregnant women (29.6% vs 24.2%, respectively). HIV-infected women were more frequently colonized by serotype III (36.4% vs 12.5%), and the majority of serotype III strains belonged to the hypervirulent clone ST-17. Exclusively trivalent vaccine serotypes (Ia, Ib, and III) were found in 57.6% and 75% of HIV-infected and -uninfected women, respectively, whereas the hexavalent vaccine serotypes (Ia, Ib, II, III, IV, and V) were found in 97% and 100%, respectively. Conclusions HIV-infected and -uninfected pregnant women living in Belgium have a similar GBS colonization rate. A trend to a higher colonization rate with serotype III was found in HIV-infected women, and those serotype III strains belong predominantly to the hypervirulent clone ST17.

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Group B streptococcal infections in infants in Iceland: clinical and microbiological factors

Journal of Medical Microbiology ◽

10.1099/jmm.0.001426 ◽

2021 ◽

Vol 70 (9) ◽

Author(s):

Birta Baeringsdottir ◽

Helga Erlendsdottir ◽

Erla Soffia Bjornsdottir ◽

Elisabete R. Martins ◽

Mário Ramirez ◽

...

Keyword(s):

Medical Records ◽

Clinical Presentation ◽

Late Onset ◽

Group B Streptococcus ◽

Surface Protein ◽

Clinical Information ◽

Neonatal Infections ◽

Presenting Symptoms ◽

Intrapartum Antibiotic ◽

Group B

Introduction. Group B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7–89 days), with different GBS clonal complexes (CCs) associated with different disease presentations. Hypothesis. Different GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia). Aim. To study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland? Methodology. All culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records. Results. A total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001). Conclusion. CC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.

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Linezolid

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.28.3.187 ◽

2009 ◽

Vol 28 (3) ◽

pp. 187-192

Author(s):

Susan Givens Bell

Keyword(s):

Very Low Birth Weight ◽

Late Onset ◽

Group B Streptococcus ◽

Neonatal Infection ◽

Research Network ◽

Coagulase Negative Staphylococcus ◽

Coagulase Negative Staphylococci ◽

Gram Positive ◽

Late Onset Sepsis ◽

Group B

THE MOST RECENT DATA FROM THE National Institute of Child Health and Human Development Neonatal Research Network revealed that in late-onset sepsis events in very low birth weight neonates proven by blood culture, 70 percent were caused by Gram-positive organisms. Coagulase-negative staphylococci accounted for 68 percent of these Gram-positive infections, and Staphylococcus aureus, Enterococcus species, and Group B Streptococcus were isolated in the remainder.1Staphylococcus epidermidis continues to be the most common coagulase-negative Staphylococcus species isolated in culture, and S. capitis, S. warneri, S. haemolyticus and S. hominis have also been implicated in neonatal infection.

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