Group B Streptococcus Strains Research Articles

Long-Term Co-Circulation of Host-Specialist and Host-Generalist Lineages of Group B Streptococcus in Brazilian Dairy Cattle with Heterogeneous Antimicrobial Resistance Profiles.

Group B Streptococcus (GBS) is a major cause of contagious bovine mastitis (CBM) in Brazil. The GBS population is composed of host-generalist and host-specialist lineages, which may differ in antimicrobial resistance (AMR) and zoonotic potential, and the surveillance of bovine GBS is crucial to developing effective CBM control and prevention measures. Here, we investigated bovine GBS isolates (n = 156) collected in Brazil between 1987 and 2021 using phenotypic testing and whole-genome sequencing to uncover the molecular epidemiology of bovine GBS. Clonal complex (CC) 61/67 was the predominant clade in the 20th century; however, it was replaced by CC91, with which it shares a most common recent ancestor, in the 21st century, despite the higher prevalence of AMR in CC61/67 than in CC91, and high selection pressure for AMR from indiscriminate antimicrobial use in the Brazilian dairy industry. CC103 also emerged as a dominant CC in the 21st century, and a considerable proportion of herds had two or more GBS strains, suggesting poor biosecurity and within-herd evolution due to the chronic nature of CBM problems. The majority of bovine GBS belonged to serotype Ia or III, which was strongly correlated with CCs. Ninety-three isolates were resistant to tetracycline (≥8 μg/mL; tetO = 57, tetM = 34 or both = 2) and forty-four were resistant to erythromycin (2.0 to >4 μg/mL; ermA = 1, ermB = 38, mechanism unidentified n = 5). Only three isolates were non-susceptible to penicillin (≥8.0 μg/mL), providing opportunities for improved antimicrobial stewardship through the use of narrow-spectrum antimicrobials for the treatment of dairy cattle. The common bovine GBS clades detected in this study have rarely been reported in humans, suggesting limited risk of interspecies transmission of GBS in Brazil. This study provides new data to support improvements to CBM and AMR control, bovine GBS vaccine design, and the management of public health risks posed by bovine GBS in Brazil.

Alterations in cell arrangements of group B streptococcus due to virulence factor expression can bias estimates of bacterial populations based on colony count measures.

Group B streptococcus (GBS) is a chain-forming commensal bacterium and opportunistic pathogen that resides in the gastrointestinal and genitourinary tract of healthy adults. GBS can cause various infections and related complications in pregnant and nonpregnant women, adults, and newborns. Investigations of the mechanisms by which GBS causes disease pathogenesis often utilize colony count assays to estimate bacterial population size in experimental models. In other streptococci, such as group A streptococcus and pneumococcus, variation in the chain length of the bacteria that can occur naturally or due to mutation can affect facets of pathogenesis, such as adherence to or colonization of a host. No studies have reported a relationship between GBS chain length and pathogenicity. Here, we used GBS strain 874391 and several derivative strains displaying longer chain-forming phenotypes (874391pgapC, 874391ΔcovR, 874391Δstp1) to assess the impact of chain length on bacterial population estimates based on the colony-forming unit (c.f.u.) assay. Disruption of GBS chains via bead beating or sonication in conjunction with fluorescence microscopy was used to compare chaining phenotypes pre- and post-disruption to detect long- and short-chain forms, respectively. We used a murine model of GBS colonization of the female reproductive tract to assess whether chaining may affect bacterial colonization dynamics in the host during chronic infection in vivo. Overall, we found that GBS exhibiting long-chain form can significantly affect population size estimates based on the colony count assay. Additionally, we found that the length of chaining of GBS can affect virulence in the reproductive tract colonization model. Collectively, these findings have implications for studies of GBS that utilize colony count assays to measure GBS populations and establish that chain length can affect infection dynamics and disease pathogenesis for this important opportunistic pathogen.

Predicting hosts and cross-species transmission of Streptococcus agalactiae by interpretable machine learning

BackgroundStreptococcus agalactiae, commonly known as Group B Streptococcus (GBS), exhibits a broad host range, manifesting as both a beneficial commensal and an opportunistic pathogen across various species. In humans, it poses significant risks, causing neonatal sepsis and meningitis, along with severe infections in adults. Additionally, it impacts livestock by inducing mastitis in bovines and contributing to epidemic mortality in fish populations. Despite its wide host spectrum, the mechanisms enabling GBS to adapt to specific hosts remain inadequately elucidated. Therefore, the development of a rapid and accurate method differentiates GBS strains associated with particular animal hosts based on genome-wide information holds immense potential. Such a tool would not only bolster the identification and containment efforts during GBS outbreaks but also deepen our comprehension of the bacteria's host adaptations spanning humans, livestock, and other natural animal reservoirs. Methods and resultsHere, we developed three machine learning models—random forest (RF), logistic regression (LR), and support vector machine (SVM) based on genome-wide mutation data. These models enabled precise prediction of the host origin of GBS, accurately distinguishing between human, bovine, fish, and pig hosts. Moreover, we conducted an interpretable machine learning using SHapley Additive exPlanations (SHAP) and variant annotation to uncover the most influential genomic features and associated genes for each host. Additionally, by meticulously examining misclassified samples, we gained valuable insights into the dynamics of host transmission and the potential for zoonotic infections. ConclusionsOur study underscores the effectiveness of random forest (RF) and logistic regression (LR) models based on mutation data for accurately predicting GBS host origins. Additionally, we identify the key features associated with each GBS host, thereby enhancing our understanding of the bacteria's host-specific adaptations.

Antimicrobial Resistance Profile of Group B Streptococci Colonization in a Sample Population of Pregnant Women from Romania.

Group B Streptococcus (GBS) represents one of the leading causes of life-threatening invasive disease in pregnant women and neonates. Rates of GBS colonization vary by region, but studies on maternal GBS status are limited in Romania. This study aims to identify the prevalence of colonization with GBS and whether the obstetrical characteristics are statistically associated with the study group's antimicrobial susceptibility patterns of tested GBS strains. This observational study was conducted between 1 May and 31 December 2021 at The Department of Obstetrics and Gynecology at Elias University Emergency Hospital (EUEH) in Bucharest, Romania. A total of 152 samples were positive for GBS and included in the study according to the inclusion criteria. As a result, the prevalence of colonized patients with GBS was 17.3%. GBS isolated in this population had the highest resistance to erythromycin (n = 38; 25%), followed by clindamycin (n = 36; 23.7%). Regarding the susceptibility patterns of tested strains to penicillin, the 152 susceptible strains had MIC breakpoints less than 0.06 μg/μL. The susceptibility patterns of tested strains to linezolid indicated three resistant strains with low levels of resistance (MICs ranging between 2 and 3 μg/μL). Multidrug resistance (at least three antibiotic classes) was not observed. In conclusion, although GBS naturally displays sensitivity to penicillin, the exact bacterial susceptibility testing should be performed in all cases where second-line therapy is taken into consideration for treatment. We acknowledge the need for future actions to limit multidrug-resistant bacteria.

Development and early testing of a simple, low cost, fast sensor for maternal and neonatal group B Streptococcus

Streptococcus agalactiae, (Group B Streptococcus (GBS)), is a common colonizer of the female vagina. In women giving birth it can be transmitted to the baby and cause serious illness and even death to the child. We have developed a biosensor comprising of phospholipids and fatty acids vesicles encapsulating high concentration, self-quenched carboxyfluorescein, which is released by the lysis of the vesicle by virulence factors expressed by GBS, becoming diluted and fluorescent. The microbial specificity of the sensor was tested against a number of GBS strains and other microbes including Candida albicans, Enterococcus faecalis and Staphylococcus epidermidis and a statistically significant response to GBS measured over these other microbes. To test the invivo efficacy of the biosensor, a pilot study using donated lower vaginal swabs from non-pregnant women was conducted, where 58 female adults were recruited. Participants donated two swabs, one which was used for the vesicle test and one for the ‘gold standard’, enriched culture media (ECM) test. An overall GBS carriage rate of 17.2% was measured using the ECM test. The vesicle biosensor test took 45 min to obtain a result, and showed a sensitivity of 83.3%, specificity of 85.7% and accuracy of 85.3%. The test accuracy is in line with current novel GBS identification tests, with the advantage of being rapid, easy to use, low-cost and able to be conducted by bedside during start of labour.

The PI3K-Akt pathway is a multifaceted regulator of the macrophage response to diverse group B Streptococcus isolates.

Group B Streptococcus (GBS), also known as Streptococcus agalactiae, is a common member of the microbial flora in healthy individuals. However, problems may arise when GBS-colonized mothers become pregnant. GBS may be transferred from a colonized mother to her newborn or developing fetus, which may result in complications such as miscarriage, pre-term birth, meningitis, pneumonia, or sepsis. Macrophages play an especially important role in the fetal and newborn response to GBS due to the limited development of the adaptive immune system early in life. The goal of this study was to expand what is currently known about how GBS manipulates macrophage cell signaling to evade the immune system and cause disease. To this end, we investigated whether the PI3K-Akt pathway was involved in several key aspects of the macrophage response to GBS. We explored whether certain GBS strains, such as sequence type (ST)-17 strains, rely on this pathway for the more rapid macrophage uptake they induce compared to other GBS strains. Our findings suggest that this pathway is, indeed, important for macrophage uptake of GBS. Consistent with these findings, we used immunofluorescence microscopy to demonstrate that more virulent strains of GBS induce more actin projections in macrophages than less virulent strains. Additionally, we explored whether PI3K-Akt signaling impacted the ability of GBS to survive within macrophages after phagocytosis and whether this pathway influenced the survival rate of macrophages themselves following GBS infection. The PI3K-Akt pathway was found to promote the survival of both macrophages and intracellular GBS following infection. We also observed that inhibition of the PI3K-Akt pathway significantly reduced GBS-mediated activation of NFκB, which is a key regulator of cell survival and inflammatory responses. Overall, these insights into strain-dependent GBS-mediated manipulation of the PI3K-Akt pathway and its downstream targets in infected macrophages may provide new insights for the development of diagnostic and therapeutic tools to combat severe GBS disease.

Prevalence of positive group B streptococcal infections among pregnant women in Najran, Saudi Arabia

Background: Group B streptococcus (GBS) is the most common bacterium to infect women during pregnancy, and vaginal GBS colonisation is a risk factor for newborn GBS illness. The presence of GBS in the woman during labour is thought to be accurately predicted by GBS detection in the final five weeks before to delivery. This study aimed to assess the prevalence of GBS genital infections among pregnant women in Najran, Saudi Arabia. Methods: This cross-sectional retrospective study was conducted at the Armed Forces Hospital in Saudi Arabia. The study included data from electronic health records of all pregnant women who were examined and tested for genitourinary GBS infection in the hospital. Data was retrieved using a pre-designed form that included characteristic of the pregnant women, the gestational age at the time of GBS testing, and swap result of GBS. For each positive GBS swap, the antibiotic sensitivity against twenty-one antibiotics was recorded. Results: A total of 2308 pregnant women were included. The mean age was 32±7 years. The prevalence of positive GBS swap was 10.4%. The average gestational age of the women who had a positive swap was 34±9 weeks. Regarding antibiotics sensitivity, Penicillin (86.7%), Ampicillin (61.8%) and cephalexin (55.6%) were among the antibiotics that showed the highest sensitivity rates. Conclusions: We found an isolation rate of 10.4% of GBS among pregnant women who attended Najran Armed Forces Hospital. We recommend more comprehensive screening programs and strict management plans to avoid antimicrobial resistance to spread among these GBS strains.

Capsule production promotes Group B Streptococcus intestinal colonization.

Late-onset disease is the most common clinical presentation of Group B Streptococcus (GBS) infection during infancy, and gastrointestinal (GI) colonization is an important precursor. Previously, we described a murine model of postnatal GBS GI colonization that resulted in sustained colonization and progression to invasive disease. Capsular polysaccharide is an important GBS virulence factor. Vaccines based on a subset of capsular serotypes are in clinical trials. However, little is known regarding the role of specific GBS capsular serotypes in GI colonization. We examined the role of GBS capsule in GI colonization using capsule-producing and acapsular strains derived from GBS strain A909 (serotype Ia) in a murine model. Using isogenic GBS strains differing only in capsular serotypes, we explored the role of specific serotypes in GI colonization by determining competitive indices during cocolonization. We found that GBS A909 colonizes the murine GI tract without causing invasive disease. In monocolonization experiments, there was colonization persistence with the capsule-producing strain (100%) compared to the acapsular mutant strain (13%). In cocolonization experiments, the capsule-producing strain outcompeted its isogenic acapsular mutant, with a geometric mean competitive index of 8, 95% confidence interval (CI) [1.7, 38.9] in the colon at 7 days post-colonization. A909 expressing its native serotype Ia capsule outcompeted an isogenic mutant that expresses serotype III capsule, with a geometric mean competitive index of 2.5, 95% CI [1.2, 5.1] in the colon at 7 days post-colonization. Thus, polysaccharide capsule production enhances GBS GI colonization in vivo. In an A909 genetic background, the production of a serotype Ia capsule provides a competitive advantage over an isogenic strain producing type III capsule. The murine model is a valuable tool to understand the role of GBS capsule types in GI colonization. IMPORTANCE The establishment of GBS intestinal colonization is believed to be a critical precursor to late-onset disease in neonates, which has a significant impact on neurodevelopment outcomes in this population. Our prior work described a murine model of postnatal Group B Streptococcus (GBS) acquisition and invasive disease. Using this model, we explored the importance of GBS polysaccharide capsule production on gastrointestinal colonization. We found that the expression of capsule (compared to isogenic acapsular strains) provides an advantage in intestinal colonization and, importantly, that capsule type Ia has an advantage over capsule type III in a GBS A909 strain background. We speculate that specific serotypes may differ in colonization fitness, which may play a role in serotype distribution in neonatal disease.

Resistance Rates of Streptococcus agalactiae Strains Isolated from Urine Samples to Various Antibiotics

Aim: Group B Streptococcus (GBS), also known as Streptococcus agalactiae, are Gram-positive, encapsulated bacteria found in the normal human gastrointestinal and urogenital flora. A wide variety of infectious diseases can cause urogenital system infections in newborns, elderly people, immunocompromised people, pregnant women, and adults. In this study, we aimed to inform clinicians about the agents that can be used in intrapartum antibiotic prophylaxis by examining the antibiotic susceptibility of GBS strains isolated from urine samples from the Gynecology and Obstetrics Clinic in our laboratory.
 Material and Methods: Isolates of the S. agalactiae isolated from a total of 222 urine samples from the Gynecology and Obstetrics Clinic that came to our Medical Microbiology laboratory between January 2022 and December 2022 were included and the data of these isolates were evaluated retrospectively. The clinical samples that came to our laboratory were inoculated on Sheep blood agar medium and incubated at 37°C for 18-24 hours. Quantitatively seeded urine culture ≥104 CFU/ml grown bacteria was considered a uropathogenic. Urogenital skin flora element or three and more different types of bacteria growing cultures as contamination evaluated. 
 Results: Due to the group selected as the sample, 100% of the patients were female. The age range of the patients ranged from 12 to 72, and the mean age was calculated as 30.16. All GBS isolates were susceptible to penicillin, linezolid, trimethoprim-sulfamethoxazole, tigecycline, teicoplanin, and vancomycin. 
 Conclusion: Penicillin resistance was not found in our study. However, resistant strains were detected in erythromycin, clindamycin, and levofloxacin, which stand out as other options in cases where penicillin cannot be used.

Near-term pregnant women in the Dominican Republic experience high rates of Group B Streptococcus rectovaginal colonization with virulent strains.

Maternal colonization with Group B Streptococcus (GBS) is an important cause of stillbirth, prematurity, and serious infection and death in infants worldwide. Resource constraints limit prevention strategies in many regions. Maternal GBS vaccines in development could be a more accessible prevention strategy, but data on geographic variations in GBS clones are needed to guide development of a broadly effective vaccine. In the Dominican Republic (DR), limited data suggest that pregnant women experience GBS colonization at rates among the highest globally. We aimed to determine the prevalence of maternal rectovaginal GBS colonization and describe clonal characteristics of colonizing strains in the DR. A cross-sectional study assessed rectovaginal GBS colonization in 350 near-term pregnant women presenting for routine prenatal care at an urban tertiary center in the DR. Rectovaginal samples were tested with chromogenic Strep B Carrot Broth and cultured for confirmatory whole-genome sequencing. In a secondary analysis, participants' demographics and histories were assessed for association with GBS colonization. Rectovaginal GBS colonization occurred in 26.6% of women. Serotypes Ia, Ib, II, III, IV, and V were detected, with no one serotype predominating; serotype III was identified most frequently (21.5%). Virulent and emerging strains were common, including CC17 (15.1%) and ST1010 (17.2%). In this first characterization of maternal GBS serotypes in the DR, we found high rates of rectovaginal colonization including with virulent and emerging GBS strains. The serotypes observed here are all targeted by candidate hexavalent GBS vaccines, suggesting effective protection in the DR.

Effect of probiotics on mother-to-neonate vertical transmission of group B streptococci: A prospective open-label randomized study

Group B Streptococci (GBS) are common vaginal bacteria found in 20-30% of pregnant women and a significant cause of invasive infections in newborns. Recently, attention has been focused on the efficacy of probiotics during the perinatal period. However, the effect of probiotic intake on the mother-to-child transmission (MTCT) of GBS remains unknown. Pregnant women with positive GBS results from vaginal and rectal swab cultures at 35-37 weeks of gestation were randomly assigned to the probiotic group or the control group in an open-label manner at the Department of Obstetrics and Gynecology, San-ikukai Hospital, Tokyo, Japan. The probiotic group received Lactobacillus reuteri during antenatal checkups from 35 to 37-week gestation to 1 month after delivery. Rectal swabs were obtained from the newborns at 5 days and at 1 month of age. Whole-genome sequencing was performed to test for GBS strains in the mother, whose newborn carried GBS at the 1-month checkup. Multi-locus sequence typing and single nucleotide polymorphism analyses were performed to identify MTCT. Overall, 67 mother-infant pairs were included, with 31 in the probiotic group and 36 in the control group. The positivity rate of GBS in newborns at 1 month of age was 10% (n=3) in the probiotic group and 28% (n=10) in the control group. In newborns carrying GBS at 1 month of age, genetic analysis revealed that the MTCT rate was 6% in the probiotic group and 22% in the control group, although the difference was not statistically significant (p=0.0927). No statistically significant difference was found; however, the consumption of L. reuteri by women with GBS-positive pregnancies may inhibit the MTCT of GBS.

The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection.

Group B Streptococcus (GBS) is a Gram-positive pathobiont that can cause adverse health outcomes in neonates and vulnerable adult populations. GBS is one of the most frequently isolated bacteria from diabetic (Db) wound infections but is rarely found in the non-diabetic (nDb) wound environment. Previously, RNA sequencing of wound tissue from Db wound infections in leprdb diabetic mice showed increased expression of neutrophil factors, and genes involved in GBS metal transport such as the zinc (Zn), manganese (Mn), and putative nickel (Ni) import systems. Here, we develop a Streptozotocin-induced diabetic wound model to evaluate the pathogenesis of two invasive strains of GBS, serotypes Ia and V. We observe an increase in metal chelators such as calprotectin (CP) and lipocalin-2 during diabetic wound infections compared to nDb. We find that CP limits GBS survival in wounds of non-diabetic mice but does not impact survival in diabetic wounds. Additionally, we utilize GBS metal transporter mutants and determine that the Zn, Mn, and putative Ni transporters in GBS are dispensable in diabetic wound infection but contributed to bacterial persistence in non-diabetic animals. Collectively, these data suggest that in non-diabetic mice, functional nutritional immunity mediated by CP is effective at mitigating GBS infection, whereas in diabetic mice, the presence of CP is not sufficient to control GBS wound persistence. IMPORTANCE Diabetic wound infections are difficult to treat and often become chronic due to an impaired immune response as well as the presence of bacterial species that establish persistent infections. Group B Streptococcus (GBS) is one of the most frequently isolated bacterial species in diabetic wound infections and, as a result, is one of the leading causes of death from skin and subcutaneous infection. However, GBS is notoriously absent in non-diabetic wounds, and little is known about why this species thrives in diabetic infection. The work herein investigates how alterations in diabetic host immunity may contribute to GBS success during diabetic wound infection.

Group B streptococci (GBS) strains evading molecular diagnostics showed novel chromosomal deletions encompassing the CAMP-factor (cfb) encoding gene.

A highly conserved fragment adjacent to the cfb gene encoding the CAMP factor is the target of PCR-based molecular diagnostic systems for the identification of S. agalactiae (group B streptococci (GBS)). Six PCR-negative, culture-positive GBS strains were whole genome sequenced to assess why they escaped molecular diagnostics. GBS strains did not constitute a clonal cluster and presented variably sized chromosomal deletions (from 7 to 33 kb) which always included the cfb gene, a finding never described before. GBS strains that escape molecular diagnostics are considered rare; however, they can cause false-negative results using molecular diagnostics alone, affecting medical decisions.

Microbiological monitoring of antibiotic resistance of strains of Streptococcus agalactiae among pregnant women

Group B Streptococcus (GBS) is the causative agent in 2–7% of all urinary tract infections (UTI), including asymptomatic bacteriuria (AB), cystitis, and pyelonephritis. We used the bacteriological quantitative method of sowing urine samples of pregnant women on Columbia agar with 5% lamb blood), Strepto B chromogenic agar and Todd Hewitt broth, identification of GBS strains with determination of sensitivity to bacitracin, hippurate hydrolysis test and CAMP test. Susceptibility to antimicrobial drugs was determined by the disk-diffusion method according to recommendations of the European Committee on Antimicrobial Susceptibility Testing. For the period of 2021, out of 3,356 urine samples of pregnant women, there were 149 samples of the investigated biomaterial with a positive result for GBS (resultancy – 4.4%). It was established that among the studied contingent, 41 strains of GBS were isolated in the first trimester of pregnancy (27.5%), in the second trimester – 59 strains (39.5%), in the third trimester – 49 strains (33.0%). It is established that out of the 149 strains of GBS, 38 strains (25.0%) were resistant to norfloxacin, 45 strains (30.0%) to erythromycin, 41 strains (28.0%) to clindamycin,125 strains (84.0%) to tetracycline, 20 strains (13.0%) to levofloxacin, 3 strains (2.0%) to nitrofurantoin. All strains of Streptococcus agalactiae were found to be sensitive to benzylpenicillin. The number of resistant strains of SGB identified from the urine of pregnant women was 47 strains. All resistant strains were resistant to at least three groups of antibacterial drugs, except beta-lactams. The results of the scientific research will allow us to obtain dynamic data on the antibiotic resistance of GBS strains in order to study the rate of development of antibiotic sensitivity of this microorganism. In the future, the research data can be used by scientists when reviewing protocols for the treatment of urinary tract infections in pregnant women.

Geographical, Temporal and Host-Species Distribution of Potentially Human-Pathogenic Group B Streptococcus in Aquaculture Species in Southeast Asia.

Group B Streptococcus (GBS) is a major pathogen of humans and aquatic species. Fish have recently been recognized as the source of severe invasive foodborne GBS disease, caused by sequence type (ST) 283, in otherwise healthy adults in Southeast Asia. Thailand and Vietnam are among the major aquaculture producers in Southeast Asia, with GBS disease reported in fish as well as frogs in both countries. Still, the distribution of potentially human-pathogenic GBS in aquaculture species is poorly known. Using 35 GBS isolates from aquatic species in Thailand collected from 2007 to 2019 and 43 isolates from tilapia collected in Vietnam in 2018 and 2019, we have demonstrated that the temporal, geographical, and host-species distribution of GBS ST283 is broader than previously known, whereas the distribution of ST7 and the poikilothermic lineage of GBS are geographically restricted. The gene encoding the human GBS virulence factor C5a peptidase, scpB, was detected in aquatic ST283 from Thailand but not in ST283 from Vietnam or in ST7 from either country, mirroring current reports of GBS strains associated with human sepsis. The observed distribution of strains and virulence genes is likely to reflect a combination of spill-over, host adaptation through the gain and loss of mobile genetic elements, and current biosecurity practices. The plastic nature of the GBS genome and its importance as a human, aquatic, and potentially foodborne pathogen suggests that active surveillance of GBS presence and its evolution in aquaculture systems may be justified.

Safety and immunogenicity of the group B streptococcus vaccine AlpN in a placebo-controlled double-blind phase 1 trial.

Group B streptococcus (GBS) is a leading cause of life-threatening neonatal infections and subsets of adverse pregnancy outcomes. Essentially all GBS strains possess one allele of the alpha-like protein (Alp) family. A maternal GBS vaccine, consisting of the fused N-terminal domains of the Alps αC and Rib (GBS-NN), was recently demonstrated to be safe and immunogenic in healthy adult women. To enhance antibody responses to all clinically relevant Alps, a second-generation vaccine has been developed (AlpN), also containing the N-terminal domain of Alp1 and the one shared by Alp2 and Alp3. In this study, the safety and immunogenicity of AlpN is assessed in a randomized, double-blind, placebo-controlled, and parallel-group phase I study, involving 60 healthy non-pregnant women. AlpN is well tolerated and elicits similarly robust and persistent antibody responses against all four Alp-N-terminal domains, resulting in enhanced opsonophagocytic killing of all Alp serotypes covered by the vaccine.

Gamma-Irradiated Non-Capsule Group B Streptococcus Promotes T-Cell Dependent Immunity and Provides a Cross-Protective Reaction.

Group B Streptococcus (GBS) is a Gram-positive bacterium commonly found in the genitourinary tract and is also a leading cause of neonatal sepsis and pneumonia. Despite the current antibiotic prophylaxis (IAP), the disease burdens of late-onset disease in newborns and non-pregnant adult infections are increasing. Recently, inactivation of the pathogens via gamma radiation has been proven to eliminate their replication ability but cause less damage to the antigenicity of the key epitopes. In this study, the non-capsule GBS strain was inactivated via radiation (Rad-GBS) or formalin (Che-GBS), and we further determined its immunogenicity and protective efficacy as vaccines. Notably, Rad-GBS was more immunogenic and gave rise to higher expression of costimulatory molecules in BMDCs in comparison with Che-GBS. Flow cytometric analysis revealed that Rad-GBS induced a stronger CD4+ IFN-γ+ and CD4+IL-17A+ population in mice. The protective efficacy was measured through challenge with the highly virulent strain CNCTC 10/84, and the adoptive transfer results further showed that the protective role is reversed by functionally neutralizing antibodies and T cells. Finally, cross-protection against challenges with prevalent serotypes of GBS was induced by Rad-GBS. The higher opsonophagocytic killing activity of sera against multiple serotypes was determined in sera from mice immunized with Rad-GBS. Overall, our results showed that the inactivated whole-cell encapsulated GBS could be an alternative strategy for universal vaccine development against invasive GBS infections.

Anti-biofilm Activity of Human Milk Oligosaccharides in Clinical Strains of Streptococcus agalactiae with Diverse Capsular and Sequence Types.

Group B Streptococcus (GBS) is an encapsulated Gram-positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short-chain sugars that have recently been shown to possess antimicrobial and anti-biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO-dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular-type- and sequence-type-specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST-1, ST-12, ST-19, and ST-23 strains. Interestingly, CpsIa as well as ST-7 and ST-17 were not susceptible to the anti-biofilm activity of HMOs, underscoring the strain-specific effects of these important antimicrobial molecules against the perinatal pathogen Streptococcus agalactiae.

Host inflammatory dynamics reveal placental immune modulation by Group B Streptococcus during pregnancy.

Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin β-hemolysin/cytolysin (β-h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of β-h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through β-h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a β-h/c-deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that β-h/c-producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge.

Molecular Epidemiology of Group B Streptococcus Colonization in Egyptian Women.

(1) Background: Streptococcus agalactiae or Group B Streptococcus (GBS) causes severe neonatal infections with a high burden of disease, especially in Africa. Maternal vaginal colonization and perinatal transmissions represent the common mode of acquiring the infection. Development of an effective maternal vaccine against GBS relies on molecular surveillance of the maternal GBS population to better understand the global distribution of GBS clones and serotypes. (2) Methods: Here, we present genomic data from a collection of colonizing GBS strains from Ismailia, Egypt that were sequenced and characterized within the global JUNO project. (3) Results: A large proportion of serotype VI, ST14 strains was discovered, a serotype which is rarely found in strain collections from the US and Europe and typically not included in the current vaccine formulations. (4) Conclusions: The molecular epidemiology of these strains clearly points to the African origin with the detection of several sequence types (STs) that have only been observed in Africa. Our data underline the importance of continuous molecular surveillance of the GBS population for future vaccine implementations.