GBS Infection Research Articles

Streptococcus agalactiae Infection in Nile Tilapia (Oreochromis niloticus): A Review

Streptococcus agalactiae (Group B Lancefield) has emerged as a significant pathogen affecting both humans and animals, including aquatic species. Infections caused by S. agalactiae are becoming a growing concern in aquaculture and have been reported globally in various freshwater and marine fish species, particularly those inhabiting warm water environments. This has led to numerous outbreaks with high morbidity and mortality in fish. Nile tilapia (Oreochromis niloticus), a member of the Cichlid family, is one of the severely affected fish species by S. agalactiae. The current study aims to focus on S. agalactiae infection in cultured O. niloticus with reference to its transmission and sources of infection; risk factors influencing GBS infection, disease clinical signs, lesions, and pathogenesis; S. agalactiae virulence factors; and how to diagnose, treat, control, and prevent infection including vaccination and herbal extract medication.

Comparison of qPCR and chromogenic culture methods for rapid detection of group B streptococcus colonization in Vietnamese pregnant women

IntroductionNeonatal infections can rapidly become severe, with delays in treatment often proving fatal. Streptococcus agalactiae (Group B Streptococcus, GBS) is a common cause, typically transmitted from colonized pregnant women to neonates during childbirth. In Vietnam, routine prenatal care lacks standardized GBS screening protocols. This study aims to compare enhanced qPCR methods with the culture method, evaluate the diagnostic accuracy of these qPCR procedures, and assess the frequency of GBS infection in pregnant Vietnamese women during their final trimester. Materials and methodsPregnant women aged 35 weeks gestation or more were recruited. Rectovaginal swabs were collected and analyzed for GBS using chromogenic culture, a commercial real-time PCR kit, and in-house real-time PCR assays targeting the cfb and sip genes. Clinical diagnostic values were calculated, and GBS prevalence was determined. ResultsThe study included 259 pregnant women with a mean age of 30.2 ± 5.0 years. Of these, 96.6 % had gestational ages of 37 weeks or more at delivery. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the cfb-based and sip-based qPCR assays were 94.1/92.7, 99.0/99.5, 97.1/98.5, 97.8/97.3, and 97.6 %, respectively. The Kappa values were excellent (0.940 and 0.939), with results available in under 2 h. GBS prevalence was 24.7 % and 25.5 % by cfb-based and sip-based qPCR assays, aligning with the culture method (25.5 %). ConclusionsBoth direct real-time PCR assays demonstrated high accuracy and were comparable to chromogenic culture in diagnosing GBS. A significant prevalence of GBS colonization was found among Vietnamese pregnant women in their final trimester.

Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections.

Rising incidence of invasive beta-haemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated. A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE or GBS. Antibody responses to six Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2log10 arbitrary units/mL (AU/mL). Sixty-seven participants were enrolled. Thirty-three participants were included in the final analysis (12, 11 and 10 with Strep A, SDSE and GBS, respectively). The median serological response for participants with Strep A was significant for all tested antigens (median >0.2log10 difference between acute and convalescent samples; P<0.05 for all). Those with SDSE had comparable and significant median (IQR) responses to streptolysin-O (0.65 [0.36-1.67], P=0.004), S. pyogenes adhesion and division protein (0.68 [0.36-1.63], P=0.005) and C5a peptidase (ScpA; 0.30 [0.23-1.06]), P=0.004). GBS responses were limited to ScpA only (0.34 [0.08-0.52], P=0.05). Patients with invasive Strep A infection mount robust antibody responses to six non-M protein vaccine candidate antigens. Similar significant responses to C5a peptidase in those with invasive SDSE and GBS infection highlight the importance of further research into cross-species protection and immunological correlates of vaccine efficacy.

Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection

IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host’s defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

Group B Streptococcus Infections in Non-Pregnant Adults, Italy, 2015-2019.

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen of increasing importance in adults. Severe and invasive cases in non-pregnant adults were collected during the period 2015-2019 by voluntary-based surveillance. In total, 108 GBS strains were phenotypically and genotypically characterized for the serotype, antimicrobial resistance, pili, surface protein genes, and the hyper-virulent adhesin hvgA. Patients were divided into two age groups: adults (18-64 years; n = 32) and older adults (≥65 years; n = 72). The average age was 70.8 years, with a male/female ratio of 1.7. Most isolates were recovered from cases of bacteremia (blood, n = 93), and a higher frequency of invasive GBS infections (iGBS) was found among older adults (66.7%). Serotype III was the most frequent (n = 41, 38%), followed by type Ia and type V (n = 20 each, 18.5%). Serotypes Ia, Ib, II, III, IV, and V accounted for all but one isolates (99.1%). The iGBS isolates were universally susceptible to penicillin, while the prevalence of resistance to clindamycin, erythromycin, tetracycline, and high-level gentamicin resistance was 26.8%, 24.1%, 85.2%, and 5.5%, respectively, with the predominance of the erm(B) gene for macrolide resistance and the tet(M) gene for tetracycline resistance. The associations between the serotypes/antimicrobial resistance/virulence traits underlined the increasing importance of serotype III and its contribution to antimicrobial resistance as well as the steady increase over time of serotype IV. This nationwide study confirmed the need for monitoring the GBS epidemiology in non-pregnant adults through continuous surveillance of GBS infections.

Multidrug Resistant Group B Streptococcus Isolates from Pregnant Women in Delta State, Nigeria.

&lt;b&gt;Background and Objective:&lt;/b&gt; Group B &lt;i&gt;Streptococci&lt;/i&gt; (GBS) are globally recognized as a major risk factor for neonatal infections and various obstetric complications. More so, biofilm formation has been suggested to be important for GBS pathogenesis. The aim of this study was to determine the prevalence and antibiotic susceptibility pattern of GBS among pregnant women and their capacity to form biofilm. &lt;b&gt;Materials and Methods:&lt;/b&gt; A total of 87 pregnant women at 34 to 37 weeks' gestation aged 17-45 years were recruited from 3 healthcare centres in Delta State, Nigeria. Cultures for the isolation of GBS were carried out using recto-vaginal swabs, according to standard microbiological methods. All strains isolated were used for susceptibility tests to various antibiotics as recommended by CLSI using the disk-diffusion method. &lt;b&gt;Results:&lt;/b&gt; The overall prevalence of GBS colonization among pregnant women was 43.6% (38/87). The &lt;u&gt;<&lt;/u&gt;30 age group had the highest rate of GBS colonization. Resistance to erythromycin and vancomycin was 48.2 and 66.4%, respectively. The fluoroquinolones had the lowest resistant rates with no isolate showing resistance to ofloxacin. Multidrug resistance (MDR) (&lt;u&gt;>&lt;/u&gt;3 drug classes) was detected in 73.7% (28/38) of the GBS isolates. All GBS isolated in this study were either strong, moderate or weak biofilm producers. However, most 28 (73.7%) were strong biofilm producers. Resistance of GBS isolates to erythromycin and vancomycin, drugs used for treating GBS infection was high. &lt;b&gt;Conclusion:&lt;/b&gt; This suggested the importance of testing antimicrobial susceptibilities in GBS colonized pregnant women in order to guide antibiotic therapy and minimize newborn infection and co-morbidity.

The SaeRS two-component system regulates virulence gene expression in group B Streptococcus during invasive infection.

Group B Streptococcus (or GBS) is a normal inhabitant of the human gastrointestinal and genital tracts that can also cause deadly infections in newborns and elderly people. The transition from a harmless commensal to a dangerous pathogen relies on the timely expression of bacterial molecules necessary for causing disease. In this study, we characterize the two-component system SaeRS as a key regulator of such virulence factors. Our analysis reveals a specialized regulatory system that is activated only during infection to dynamically adjust the production of two virulence factors involved in interactions with host cells. Overall, our findings highlight the critical role of SaeRS in GBS infections and suggest that targeting this system may be useful for developing new antibacterial drugs.

Behavioral dysregulation in Nile tilapia (Oreochromis niloticus, GIFT) post-Streptococcus agalactia infection: Role of the microbiota-gut-brain axis

In the aquatic farming industry, understanding the factors affecting fish behavior is crucial, particularly in response to infections that compromise welfare and productivity. Swimming performance is a key life history trait critical to their ecology. This study explores the swimming behavior imbalance in Nile tilapia (Oreochromis niloticus, GIFT) post-infection with Streptococcus agalactiae (GBS), a common pathogen responsible for significant losses in aquaculture. We focused on how the microbiota-gut-brain axis influences the behavioral response of tilapia to GBS infection. Behavioral changes were quantified by measuring collision times and swimming speeds, which decreased significantly following infection. This behavioral downturn is mediated by alterations in the microbiota-gut-brain axis, evidenced by increased levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain and intestinal tissues. The study utilized pharmacological agents, the 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635), to investigate their efficacy in mitigating these behavioral and biochemical changes. Both agents partially restored normal behavior by adjusting neurotransmitter concentrations disrupted by GBS infection. Additionally, a notable increase in the relative abundance of Streptococcus within the gut microbiota of infected fish highlights the potential role of specific bacterial populations in influencing host behavior. This research provides novel insights into the complex interactions between pathogen-induced gut microbiota changes and Nile tilapia's behavioral outcomes, highlighting potential avenues for improving fish health management through microbiota-targeted interventions.

Molecular epidemiology and virulence factors of group B Streptococcus in South Korea according to the invasiveness

BackgroundGroup B Streptococcus (GBS) causes invasive infections in newborns and elderly individuals, but is a noninvasive commensal bacterium in most immunocompetent people. Recently, the incidence of invasive GBS infections has increased worldwide, and there is growing interest in the molecular genetic characteristics of invasive GBS strains. Vaccines against GBS are expected in the near future. Here, we aimed to analyze the molecular epidemiology of GBS according to the invasiveness in South Korea.MethodsWe analyzed GBS isolates collected and stored in two hospitals in South Korea between January 2015 and December 2020. The invasiveness of these isolates was determined via a retrospective review of clinical episodes. Totally, 120 GBS isolates from 55 children and 65 adults were analyzed. Serotype and sequence type (ST) were determined using multiplex polymerase chain reaction (PCR) and multilocus sequence typing, respectively. Fourteen virulence factor-encoding genes of GBS were analyzed using multiplex PCR.ResultsForty one (34.2%) were invasive infection-related GBS isolates (iGBS). The most frequently detected serotype was III (39/120, 32.5%), and it accounted for a high proportion of iGBS (21/41, 51.2%). The most frequent ST was ST19 (18/120, 15.0%), followed by ST2 (17/120, 14.2%). Serotype III/ST17 was predominant in iGBS (12/41, 29.3%), and all 17 ST2 strains were noninvasive. The distribution of most of the investigated virulence factors was not significantly related to invasiveness; noteworthily, most of the serotype III/ST17 iGBS carried pilus island (PI) 2b (10/12, 83.3%), and the prevalence of fbsB was significantly low compared with noninvasive GBS isolates (P = 0.004). Characteristically, the combination of bca(+)-cspA(+)-pavA(+)-fbsB(-)-rib(+)-bac(-) was predominant in iGBS (24.4%, 10/41).ConclusionsSerotype III/ST17 GBS carrying PI-2b was frequently detected in iGBS. There was no significant association between invasiveness and the pattern of virulence factors; however, a specific combination of virulence factors was predominant in iGBS.

Whole Genome Sequencing for the Identification of a Streptococcus agalactiae Outbreak in Neonatal Intensive Care Unit

Background: While Streptococcus agalactiae (Group B Streptococcus [GBS]) infections in infants usually result from maternal transmission, healthcare-associated cases, particularly in the neonatal intensive care unit (NICU), can occur. Whole genome sequencing (WGS) can aid in investigating GBS outbreaks among infants in hospital settings. The aim of the study is to describe the investigation of GBS infections in NICU using WGS. Methods: Infection prevention and control (IPAC) at our hospital monitors the occurrence of late-onset GBS disease (LOD) in our 57-bed NICU, which consists of all private rooms. The occurrence of 2 cases of LOD within 2 weeks triggered an investigation, including WGS of the two isolates and isolates causing invasive GBS during the last 6 months in the unit. GBS isolates underwent WGS using Illumina at Canada’s National Microbiology Laboratory. All affected patients underwent chart-review. Outbreak description and investigation: In August 2023, two NICU neonates (patients 2,3) experienced LOD two weeks apart, one with bacteremic meningitis and the other with two bacteremic episodes three weeks apart. While WGS was pending two additional cases of late-onset GBS bacteremia (patients 4,5) occurred. Isolates from Pts 2,3 and 5 were indistinguishable from each other and from an isolate from an infant admitted to the NICU with early onset bacteremia on July 27, 2023 (day 1 of life) (patient 1). Weekly point prevalence for throat and rectal colonization over 3 weeks identified five infants colonized with unrelated strains. An additional long-stay infant (patient 6) developed GBS conjunctivitis due to a strain indistinguishable from (patient 4) by pulse field gel electrophoresis, WGS for the second cluster is pending. IPAC interventions: Lapses in IPAC practices were observed, with no commonalities among cases other than similar geographic location within the unit. We hypothesized transmission was due to horizontal transmission between babies due to these lapses. Basic IPAC measures, including hand hygiene and environmental cleaning, were reinforced; Additional Precautions were not used due to private rooms’ unit structure. No environmental samples were taken due to lack of an obvious environmental point or common source. Point prevalence monitoring persisted until no new cases related to the outbreak strains were further identified in three consecutive weekly point prevalence. Conclusions: Increased awareness of healthcare-associated transmission is crucial in NICU as LOD GBS emerges. WGS plays a key role in identifying transmission. Detecting a multi-strain outbreak can appropriately redirect investigations. Legend: Figure 1: Timeline of stay at NICU and infection timing for patients 1-6

Resistance of juvenile Nile tilapia Oreochromis niloticus from Brazilian populations to Streptococcus agalactiae (serotype Ib and ST-NT)

Nile tilapia is the main farmed fish in Brazilian aquaculture. Streptococcus agalactiae (GBS) is responsible for high mortality rates in fish farms. Genetic improvement is considered an effective alternative for producing resistant animals in aquaculture. The objective of this study was to estimate genetic parameters for resistance to GBS infection in a breeding population of Nile tilapia from Brazil, based on disease challenge using a circulating serotype (Ib and ST-NT). Furthermore, genetic correlations between resistance to GBS and average daily gain (ADG) were estimated to determine whether these traits can be included in selective breeding programs. Survival (SS) and time until death (TD) were the evaluated traits. The survival of the most resistant families was approximately 30%, indicating high phenotypic variation in resistance to the infection. Low to moderate heritability values for resistance traits in the Nile tilapia population were estimated, ranging from 0.14 to 0.27. Heritability for ADG was moderate to high (0.40) based on a growth trial involving 43 families (735 animals). Phenotypic correlations between the resistance traits (SS and TD) and ADG were positive and low, ranging from 0.09 to 0.18, whereas genetic correlations were close to zero. Phenotypic and genetic correlations between SS and TD were considered high and positive, ranging from 0.38 to 0.72. The results suggest that selection for resistance against GBS does not negatively affect juvenile weight gain in Nile tilapia.

Group B Streptococcus Infection and Obstetric Hemorrhage Risk.

To elucidate the association between GBS infection and maternal risk for obstetric hemorrhage (OBH) and OBH-related morbidities (OBH-M). This was a retrospective cohort study of all deliveries with a documented GBS status at a single large academic medical center from 2018 to 2019. GBS status was determined by either urine culture or rectovaginal culture collected during the antepartum period. The primary outcomes were quantitative blood loss (QBL), OBH, and a composite of OBH-M. Secondary outcomes were individual components of the OBH-M composite and frequency of hemorrhage-related interventions utilized intrapartum and postpartum. A stratified analysis was conducted examining only patients who were diagnosed intrapartum with an intrapartum intraamniotic infection (III). Of 4679 pregnant individuals who delivered a live infant between January 1, 2018 and January 1,2019 with a documented GBS status, 1,487 were identified as GBS positive (+) and 3192 were identified as GBS negative (-). The GBS + group did not have significantly higher QBL (p = 0.29) or rate of OBH (p = 0.35). There were no significant differences by GBS status in OBH morbidity (p = 0.79) or its individual components or frequency of individual pharmacologic or non-pharmacologic OBHrelated interventions. There were also no significant differences by GBS status among patients with an III. GBS infection at the time of delivery was not associated with increased risk for OBH or OBH-M. Further research is needed to further explore the relationship between peripartum infections and OBH risk.

Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.

Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model.

Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints. Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests. Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1β, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05). Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.

Adherence to universal screening for group B Streptococcus in pregnancy and prevalence of colonised pregnancies in Caserta province, Italy.

Group B Streptococcus (Streptococcus agalactiae; GBS) infection is a significant contributor to neonatal morbidity and mortality. In the early 1970s, the neonatal mortality rate for infants with invasive GBS disease was 55%. With the adoption of the first medical community guidelines to prevent GBS infection in the 1990s, the mortality rate decreased to approximately 5%. The main obstetric procedure for preventing vertical transmission of GBS infection involves universal screening of pregnant women using a vaginal-rectal swab (VRS) to identify those eligible for intrapartum antibiotic prophylaxis (IAP). The study analyzes the adherence of screening and the trend of GBS infection in pregnancy in the province of Caserta, Italy. Data were obtained from pregnant women who gave birth in a first level birthing center in 2022 from birth assistance certificate (CEDAP), obstetric and neonatal record. Postnatal evaluation collected through computer-assisted telephone interviews. 567 women delivered at our center during the study period. The average coverage of GBS testing in pregnancy was 99.2% (562), and the proportion of GBS colonised women was 12.6% (71) according with the national average, which is about 10-20%. The spread of positive cases appears to fluctuate among the various groups of pregnant women studied, indicating no significant statistical variance among presence of a partner, among women who have given birth multiple times, among Italian nationals, or across different ages, but a significant statistical excess is evident among mothers with less education. In 93% (66) of GBS carrier mothers, intrapartum antibiotic prophylaxis (IAP) was administered correctly, regardless of the type of delivery performed. Despite the successful integration of GBS screening, a significant gap remains between the ideal scenario and the actual implementation of IAP. At the three-month assessment, no child required hospitalization, consistent with the relatively low incidence of invasive GBS infection. Nevertheless, for those who are not eligible to VRS screening, such as preterm birth, or IAP, as in precipitous birth, the identification of biomarkers enabling early recognition of invasive GBS disease remains essential. Additionally, the emergence of vaccines administered during gestation, conferring passive immunity to newborns represents a promising possible new direction. Therefore, to ensure the practical application of GBS screening and actual IAP by healthcare providers, periodic audits and regular monitoring should be encouraged.

The antioxidant N-acetyl cysteine inhibits cytokine and prostaglandin release in human fetal membranes stimulated ex vivo with lipoteichoic acid or live group B streptococcus.

Infection during pregnancy is a significant public health concern due to the increased risk of adverse birth outcomes. Group B Streptococcus or Streptococcus agalactiae (GBS) stands out as a major bacterial cause of neonatal morbidity and mortality. We aimed to explore the involvement of reactive oxygen species (ROS) and oxidative stress pathways in pro-inflammatory responses within human fetal membrane tissue, the target tissue of acute bacterial chorioamnionitis. We reanalyzed transcriptomic data from fetal membrane explants inoculated with GBS to assess the impact of GBS on oxidative stress and ROS genes/pathways. We conducted pathway enrichment analysis of transcriptomic data using the Database for Annotation, Visualization and Integrated Discovery (DAVID), a web-based functional annotation/pathway enrichment tool. Subsequently, we conducted ex vivo experiments to test the hypothesis that antioxidant treatment could inhibit pathogen-stimulated inflammatory responses in fetal membranes. Using DAVID analysis, we found significant enrichment of pathways related to oxidative stress or ROS in GBS-inoculated human fetal membranes, for example, "Response to Oxidative Stress" (FDR=0.02) and "Positive Regulation of Reactive Oxygen Species Metabolic Process" (FDR=2.6*10-4 ). There were 31 significantly changed genes associated with these pathways, most of which were upregulated after GBS inoculation. In ex vivo experiments with choriodecidual membrane explants, our study showed that co-treatment with N-acetylcysteine (NAC) effectively suppressed the release of pro-inflammatory cytokines (IL-6, IL-8, TNF-α) and prostaglandin PGE2, compared to GBS-treated explants (p<.05 compared to GBS-treated samples without NAC co-treatment). Furthermore, NAC treatment inhibited the release of cytokines and PGE2 stimulated by lipoteichoic acid (LTA) and lipopolysaccharide (LPS) in whole membrane explants (p<.05 compared to LTA or LPS-treated samples without NAC co-treatment). Our study sheds light on the potential roles of ROS in governing the innate immune response to GBS infection, offering insights for developing strategies to mitigate GBS-related adverse outcomes.

The Group A Streptococcal Vaccine Candidate VAX-A1 Protects against Group B Streptococcus Infection via Cross-Reactive IgG Targeting Virulence Factor C5a Peptidase.

Group B Streptococcus (Streptococcus agalactiae or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor for severe fetal and neonatal infections as well as preterm birth, low birth weight, and neurodevelopmental abnormalities. Current clinical interventions for GBS infection are limited to antibiotics, and no vaccine is available. We previously described VAX-A1 as a highly effective conjugate vaccine against group A Streptococcus that is formulated with three antigens, SpyAD, streptolysin O, and C5a peptidase (ScpA). ScpA is a surface-expressed, well-characterized GAS virulence factor that shares nearly identical sequences with the lesser studied GBS homolog ScpB. Here, we show that GBS C5a peptidase ScpB cleaves human complement factor C5a and contributes to disease severity in the murine models of pneumonia and sepsis. Furthermore, antibodies elicited by GAS C5a peptidase bind to GBS in an ScpB-dependent manner, and VAX-A1 immunization protects mice against lethal GBS heterologous challenge. These findings support the contribution of ScpB to GBS virulence and underscore the importance of choosing vaccine antigens; a universal GAS vaccine such as VAX-A1 whose formulation includes GAS C5a peptidase may have additional benefits through some measure of cross-protection against GBS infections.

Efficacy of Cefazolin in the Treatment of Pregnancy and Vaginal GBS Infection and Its Influence on Inflammation and Maternal and Infant Outcomes

Efficacy of Cefazolin in the Treatment of Pregnancy and Vaginal GBS Infection and Its Influence on Inflammation and Maternal and Infant Outcomes

Dysregulated monocyte-derived macrophage response to Group B Streptococcus in newborns.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading pathogen of neonatal sepsis. The host-pathogen interactions underlying the progression to life-threatening infection in newborns are incompletely understood. Macrophages are first line in host defenses against GBS, contributing to the initiation, amplification, and termination of immune responses. The goal of this study was to compare the response of newborn and adult monocyte-derived macrophages (MDMs) to GBS. Monocytes from umbilical cord blood of healthy term newborns and from peripheral blood of healthy adult subjects were cultured with M-CSF to induce MDMs. M-CSF-MDMs, GM-CSF- and IFNγ-activated MDMs were exposed to GBS COH1, a reference strain for neonatal sepsis. GBS induced a greater release of IL-1β, IL-6, IL-10, IL-12p70 and IL-23 in newborn compared to adult MDMs, while IL-18, IL-21, IL-22, TNF, RANTES/CCL5, MCP-1/CCL2 and IL-8/CXCL8 were released at similar levels. MDM responses to GBS were strongly influenced by conditions of activation and were distinct from those to synthetic bacterial lipopeptides and lipopolysaccharides. Under similar conditions of opsonization, newborn MDMs phagocytosed and killed GBS as efficiently as adult MDMs. Altogether, the production of excessive levels of Th1- (IL-12p70), Th17-related (IL-1β, IL-6, IL-23) and anti-inflammatory (IL-10) cytokines is consistent with a dysregulated response to GBS in newborns. The high responsiveness of newborn MDMs may play a role in the progression of GBS infection in newborns, possibly contributing to the development of life-threatening organ dysfunction.

Group B Streptococcus vaccines: progress and potential

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen that causes sepsis and meningitis, particularly in newborns, as well as severe infections in the elderly and those at high risk. For many years, the administration of intrapartum antimicrobial prophylaxis (IAP) has been a standard method to prevent neonatal GBS infection. However, IAP may be unsuitable in low-income settings due to its high cost and difficult accessibility to medical institutions. Additionally, IAP may lead to the emergence of antimicrobial-resistant bacteria. Hence, an alternative method for the control of GBS, such as a vaccine, is needed. An effective vaccine will likely prevent the further spread of GBS and be cost-effective compared with IAP. GBS vaccines have been under development for the past two decades, and several candidates have shown potential. In this review, we discuss the current development of GBS vaccines, including types and their implementation in different target populations.