Immunogenic Proteins of Group B Streptococcus—Potential Antigens in Immunodiagnostic Assay for GBS Detection

Streptococcus agalactiae (Group B Streptococcus, GBS) is an opportunistic pathogen, which asymptomatically colonizes the gastrointestinal and genitourinary tract of up to one third of healthy adults. Nevertheless, GBS carriage in pregnant women may lead to several health issues in newborns causing life threatening infection, such as sepsis, pneumonia or meningitis. Recommended GBS screening in pregnant women significantly reduced morbidity and mortality in infants. Nevertheless, intrapartum antibiotic prophylaxis, recommended following the detection of carriage or in case of lack of a carriage test result for pregnant women who demonstrate certain risk factors, led to the expansion of the adverse phenomenon of bacterial resistance to antibiotics. In our paper, we reviewed some immunogenic GBS proteins, i.e., Alp family proteins, β protein, Lmb, Sip, BibA, FsbA, ScpB, enolase, elongation factor Tu, IMPDH, and GroEL, which possess features characteristic of good candidates for immunodiagnostic assays for GBS carriage detection, such as immunoreactivity and specificity. We assume that they can be used as an alternative diagnostic method to the presently recommended bacteriological cultivation and MALDI.

Group B Streptococcus CAMP Factor Does Not Contribute to Interactions with the Vaginal Epithelium and Is Dispensable for Vaginal Colonization in Mice

Group B Streptococcus (GBS) remains a pervasive pathogen for pregnant women and their newborns. Maternal screening and intrapartum antibiotic prophylaxis to GBS-positive mothers have reduced, but not eliminated GBS neonatal disease, and have not impacted GBS-associated preterm birth or stillbirth.

Impact of Intrapartum Antibiotic Prophylaxis on Offspring Microbiota

Infants are born into a world filled with microbes and must adapt without undue immune response while exploiting the microbiota's ability to produce otherwise unavailable nutrients. The process by which humans and microbes establish this relationship has only recently begun to be studied with the aid of genomic methods. Nearly half of all pregnant women receive antibiotics during gestation to prevent maternal and neonatal infection. Though this has been largely successful in reducing early-onset sepsis, we have yet to understand the long-term consequences of antibiotic administration during gestation to developing infants. Studies involving antibiotic use in infants suggest that dysbiosis during this period is associated with increased obesity, allergy, autoimmunity, and chronic diseases in adulthood, however, research around the limited doses of intravenous antibiotics used for intrapartum prophylaxis is limited. In this mini review, we focused on the state of the science regarding the effects of intrapartum antibiotic prophylaxis on the newborn microbial colonization process. Although, the literature indicates that there is wide variety in the specific bacteria that colonize infants from birth, limited parenteral antibiotic administration prior to delivery consistently affects the microbiota of infants by decreasing bacteria in the phylum Bacteroidetes and increasing bacteria in the phylum Proteobacteria, thus altering the normal pattern of colonization that infants experience. Delivery by cesarean section and formula feeding magnify and prolong this effect. Our mini review shows that the impact of intravenous antibiotic administration during gestation has on early colonization, growth, or immune programming in the developing offspring has not been well studied in human or animal models.

Maternal Intrapartum Antibiotic Treatment and Gut Microbiota Development in Healthy Term Infants

<b><i>Objective:</i></b> The aim of the study was to investigate the impact of intrapartum antibiotic treatment (IAT) on the compositional development of gut microbiota in healthy term infants. <b><i>Study Design:</i></b> A case-control study of 24 infants exposed to and 24 matched infants not exposed to IAT was conducted. All subjects were born by vaginal delivery at term and breastfed. None of the infants received antibiotics during the immediate neonatal period. Fecal samples were obtained at the ages of 1 and 6 months. The composition of the intestinal microbiota was assessed by 16S rRNA gene sequencing. <b><i>Results:</i></b> IAT was associated with reduced microbial richness but not diversity at 1 month of age. Furthermore, the relative abundances of Clostridiaceae and Erysipelotrichaceae were significantly altered in infants exposed to IAT as compared to nonexposed infants at 1 month of age. The observed deviations in gut microbiota composition between infants exposed and not exposed to IAT diminished by the age of 6 months. <b><i>Conclusions:</i></b> IAT is associated with short-term perturbations in the gut microbiota development in healthy term, vaginally delivered, breastfed infants. The composition of the gut microbiota is mostly restored by the age of 6 months.

Virulence and pathogenicity factors of S. agalactiae strains isolated from pregnant women and newborns

BACKGROUND: Obstetric and neonatal infections caused by Steptococcus agalactiae are among the most significant perinatal infections. To date, intrapartum antibiotic prophylaxis is used to prevent the transmission of the pathogen to the child, however, the growth of antibiotic resistance and ineffectiveness of therapy against late-onset neonatal infection are its limitations. Vaccination is considered to be the most effective method for preventing diseases caused by S. agalactiae in both pregnant women and newborn babies. To identify promising vaccine targets and to develop alternative prevention approaches, it is necessary to study the virulence factors of S. agalactiae strains and their variability in the population. AIM: The aim of this study was to evaluate the variability of virulence and pathogenicity factors (capsular polysaccharides, pili, hypervirulent sequence type ST-17, biofilm-forming ability, antibiotic resistance) of S. agalactiae isolated from pregnant women and newborn infants in St. Petersburg, Russia. MATERIALS AND METHODS: We studied isolates of S. agalactiae out of clinical material samples obtained from pregnant women and newborns at the D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology in 2018-2020. The PCR method was used to determine the types of capsular polysaccharides, pili, and strain affiliation with the hypervirulent sequencing type ST-17. Biofilm-forming ability was determined by the Christensen method. The antibiotic sensitivity was determined by disc diffusion. RESULTS: We examined 60 clinical isolates of S. agalactiae. The most common S. agalactiae serotypes were Ia, Ib, II, III, IV, and V; in total, these six serotypes accounted for 95.1% of all strains. The most common pili genotype was PI-1 + PI-2a (60%). Resistance to erythromycin was found in 36.7% of the strains, and a similar number of the strains were resistant to clindamycin. The ability to form biofilms was detected in 68% of the strains, and the increased ability was associated with the PI-2b pili allele. CONCLUSIONS: A hexavalent vaccine based on capsular polysaccharides of types Ia, Ib, II, III, IV, and V would have a 95% efficacy in this region. Stable distribution of different pili types is an important factor when using pili as vaccine targets. The high level of resistance of S. agalactiae strains to erythromycin and clindamycin indicates that isolates should be tested for sensitivity to these antibiotics before their use, and regular regional monitoring of antibiotic resistance of the pathogen to update clinical guidelines should be performed.

Need for Intrapartum Antibiotic Prophylaxis in Women with Prior History of Group B Streptococcus Carriage

The incidence of early onset neonatal GBS(EOGBS) disease in the UK and Ireland is 0.57/1000 births. Intrapartum antibiotic prophylaxis (IAP) reduces the risk. Previous colonisation is associated with 50% carriage in the current pregnancy. In these women, RCOG recommends IAP with a history of neonatal infection, otherwise offering the option of screening at 35-37 weeks. In Ireland, there is no national consensus on IAP in prior GBS colonisation. Currently at University Hospital Waterford (UHW), all women with prior GBS colonisation receive IAP. Studies examining the use of point-of-care testing have shown reduction in the use of IAP and EOGBS rates. We aimed to examine the screening and IAP administration in maternal prior GBS colonisation and the incidence of GBS in this cohort in UHW. Data was collected retrospectively from laboratory, medical records and electronic patient manager systems. Women who received IAP between 1stJuly 2020 and 31stDecember 2020 were identified. Women who received IAP for current and prior GBS colonisation were included. Women who received IAP for preterm labour, preterm prelabour rupture of membranes and pyrexia in labour were excluded. Ninety-two women with current or prior GBS colonisation received IAP, of which only 15(16.30%) were current and 77(83.69%) were prior GBS colonisation. In women with prior GBS colonisation, 49(63.63%) were screened, 3/49(6.12%) were positive, 28 were not screened. Seventy-eight (84.78%) received benzyl-penicillin. Six (6.52%) received clindamycin. Twenty-two (23.91%) babies were admitted to the Neonatal Unit, however, only one cultured positive for gram-positive cocci. The incidence of EOGBS in this cohort is low. A risk-based approach or point-of-care testing should be considered to reduce unnecessary IAP administration.

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

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.

Impact of Delivery Mode on Infant Gut Microbiota

Microbial colonization of the neonate is an important feature of normal birth. The gut microbiota has a central role in the programming of the host’s metabolism and immune function, with both immediate and long-term health consequences. During vaginal birth, the infant is exposed to diverse maternal microbes, of which specific faecal microbes colonize the infant’s gut. C-section eliminates the infant’s contact with maternal microbes, preventing vertical transmission of gut microbes. Consequently, infants are colonized by bacteria from the environment, including potential pathogens from the hospital environment. Recent studies have shown that intrapartum antibiotic exposure has a C-section-like effect on the infant gut microbiota. While the composition of the gut microbiota largely normalizes during the first year of life, epidemiological studies suggest that the aberrant early microbial exposures have long-term immunological and metabolic consequences. Because of the high prevalence of procedures that prevent normal gut microbiota development, effective methods to normalize the gut microbiota of neonates are urgently needed. Even more importantly, attention should be paid to the microbiota imbalance in C-section-born and antibiotic-exposed infants in clinical practice. Breastfeeding and probiotics are particularly important for infants with disrupted gut colonization.