Group B Streptococcal Colonization in African Countries: Prevalence, Capsular Serotypes, and Molecular Sequence Types.
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ABSTRACT:
SUBMITTER: Shabayek S
PROVIDER: S-EPMC8706430 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development.MethodsWe conducted systematic reviews and meta-analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0-90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001-2018). For these at-risk population groups, we summarised reported MLST and surface proteins.ResultsBased on 198 studies (29247isolates), 93-99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35-47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6-13),(4%; 95%CI:0-11) infant colonisation, and adult invasive disease (4%, 95%CI:2-6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains.DiscussionA hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design.
| S-EPMC7526974 | biostudies-literature
Project description:BackgroundIn non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year (2017-2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the presence of GBS clusters with specific phenotypic and genotypic patterns in this population.MethodsGBS screening was performed by using vaginal swabs collected during routine examination from women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were characterized for antibiotic resistance profile, serotype and sequence type (ST).ResultsThe GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously reported in pregnant women (around 20%). We could not find any association between participants' characteristics, previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and clindamycin were associated with the ST1 genetic background of ST1.ConclusionsOur findings indicate a similar colonization rate for pregnant and elderly women.Trial registrationCurrent Controlled Trial ISRCTN15468519 ; 06/01/2017.
| S-EPMC8091692 | biostudies-literature
Project description:The M-protein genes (emm genes) of 103 separate impetiginous Streptococcus pyogenes isolates were sequenced and the sequence types were compared to the types obtained by Vir typing. Vir typing is based on restriction fragment length polymorphism (RFLP) analysis of a 4- to 7-kb pathogenicity island encoding emm and other virulence genes. By using both HaeIII and HinfI to generate RFLP profiles, complete concordance between Vir type and emm sequence type was found. Comparison of the emm sequences with those in GenBank revealed new sequence types sharing less than 90% identity with known types. Diversity in the emm sequence was generated by corrected frameshift mutations, point mutations, and small in-frame mutations.
| S-EPMC104658 | biostudies-literature
Project description:Group B Streptococcus (GBS) is a major opportunistic pathogen in certain adult populations, including pregnant women, and remains a leading etiologic agent of newborn disease. During pregnancy, GBS asymptomatically colonizes the vaginal tract of 20-30% of healthy women, but can be transmitted to the neonate in utero or during birth resulting in neonatal pneumonia, sepsis, meningitis, and subsequently 10-15% mortality regardless of antibiotic treatment. While various GBS virulence factors have been implicated in vaginal colonization and invasive disease, the regulation of many of these factors remains unclear. Recently, CRISPR-associated protein-9 (Cas9), an endonuclease known for its role in CRISPR/Cas immunity, has also been observed to modulate virulence in a number of bacterial pathogens. However, the role of Cas9 in GBS colonization and disease pathogenesis has not been well-studied. We performed allelic replacement of cas9 in GBS human clinical isolates of the hypervirulent sequence-type 17 strain lineage to generate isogenic ?cas9 mutants. Compared to parental strains, ?cas9 mutants were attenuated in murine models of hematogenous meningitis and vaginal colonization and exhibited significantly decreased invasion of human brain endothelium and adherence to vaginal epithelium. To determine if Cas9 alters transcription in GBS, we performed RNA-Seq analysis and found that 353 genes (>17% of the GBS genome) were differentially expressed between the parental WT and ?cas9 mutant strain. Significantly dysregulated genes included those encoding predicted virulence factors, metabolic factors, two-component systems (TCS), and factors important for cell wall formation. These findings were confirmed by qRT-PCR and suggest that Cas9 may regulate a significant portion of the GBS genome. We studied one of the TCS regulators, CiaR, that was significantly downregulated in the ?cas9 mutant strain. RNA-Seq analysis of the WT and ?ciaR strains demonstrated that almost all CiaR-regulated genes were also significantly regulated by Cas9, suggesting that Cas9 may modulate GBS gene expression through other regulators. Further we show that CiaR contributes to GBS vaginal colonization and persistence. Altogether, these data highlight the potential complexity and importance of the non-canonical function of Cas9 in GBS colonization and disease.
| S-EPMC6712506 | biostudies-literature
Project description:Streptococcus pyogenes (group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone is one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. The oral epithelial tract is a niche highly abundant in glycosylated structures, particularly those of the ABO(H) blood group antigen family. Using a high-throughput approach, we determined that a strain representative of the globally disseminated M1T1 GAS clone 5448 interacts with numerous, structurally diverse glycans. Preeminent among GAS virulence factors is the surface-expressed M protein. M1 protein showed high affinity for several terminal galactose blood group antigen structures. Deletion mutagenesis shows that M1 protein mediates glycan binding via its B repeat domains. Association of M1T1 GAS with oral epithelial cells varied significantly as a result of phenotypic differences in blood group antigen expression, with significantly higher adherence to those cells expressing H antigen structures compared to cells expressing A, B, or AB antigen structures. These data suggest a novel mechanism for GAS attachment to host cells and propose a link between host blood group antigen expression and M1T1 GAS colonization. IMPORTANCE:There has been a resurgence in group A streptococcal (GAS) invasive disease, which has been paralleled by the emergence of the highly virulent M1T1 GAS clone. Intensive research has focused on mechanisms that contribute to the invasive nature of this serotype, while the mechanisms that contribute to host susceptibility to disease and bacterial colonization and persistence are still poorly understood. The M1T1 GAS clone is frequently isolated from the throat, an environment highly abundant in blood group antigen structures. This work examined the interaction of the M1 protein, the preeminent GAS surface protein, against a wide range of host-expressed glycan structures. Our data suggest that susceptibility to infection by GAS in the oral tract may correlate with phenotypic differences in host blood group antigen expression. Thus, variations in host blood group antigen expression may serve as a selective pressure contributing to the dissemination and overrepresentation of M1T1 GAS.
| S-EPMC5263248 | biostudies-literature
Project description:BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) is one of the major bacterial pathogens responsible for neonatal sepsis. Whole genome sequencing has, in recent years, emerged as a reliable tool for capsular typing and antimicrobial resistance prediction. This study characterized vaginal and rectal isolates of Group B Streptococcus obtained from pregnant women in Port Harcourt, Nigeria using a whole-genome sequence-based approach.ResultsCapsular types Ia, Ib, II, III, IV and V were detected among the 43 isolates sequenced. Twelve sequence types (STs) were identified, with ST19 (n = 9, 27.3 %) and ST486 (n = 5, 15.2 %) the most frequent among non-duplicated isolates. Of the alpha-like proteins (alp) identified, Alp1 was the most prevalent in 11 (33.3 %) isolates. Macrolide and lincosamide resistance determinants were present in 15 (45.5 %) isolates; ermB was detected in 1 (3 %), ermTR in 7 (21.2 %) isolates, lnu gene was detected in 6 (18.2 %) and mef was identified in 3 (9.1 %) isolates. Resistance of GBS to erythromycin and clindamycin (predicted from presence of erm or mef genes) was found to be 30.3 % and 24.2 %, respectively. All isolates were predicted resistant to tetracycline with only the tetM gene identified. Fluoroquinolone-resistance conferring substitutions in gyrA + parC were detected in 9 (27.3 %) isolates and chloramphenicol resistance was predicted from presence of aac6'-aph2 gene in 11 (33.3 %).ConclusionsThe data available from the whole genome sequencing of these isolates offers a small but insightful description of common serotypes and resistance features within colonizing GBS in Nigeria.
| S-EPMC8382210 | biostudies-literature
Project description:The study of surface protein antigens of group B streptococci (GBS) is important for understanding of the pathogenesis and epidemiology of infection, and several of these antigens have been proposed as components of GBS conjugate vaccines. In a previous study, we developed a novel PCR-and-sequencing system for identification of GBS serotypes and serosubtypes based on the capsular polysaccharide synthesis (cps) gene cluster. In this study, we used published sequences to develop PCR assays for identification of genes encoding GBS surface proteins including C alpha (bca), C alpha-like proteins 2 and 3 (alp2 and alp3), Rib (rib), and C beta (bac). We showed that the prototype R reference strain, Prague 25/60, contained a novel alpha-like protein antigen gene (the proposed alp4), which presumably encodes an atypical, but antigenically similar, R-like protein. Initial evaluation of these gene-specific assays showed excellent specificity. By combining cps serotypes, serosubtypes, and surface protein gene profiles, we were able to divide 224 GBS isolates into 31 serovariants. GBS bac-positive strains could be further subtyped into 11 groups and 20 subgroups. Our results confirmed and extended reported associations between some cps serotypes and serosubtypes, on the one hand, and surface protein genes, on the other: serosubtypes III-1 and III-2 were associated with rib, serosubtype III-3 with alp2, serotype Ib with bca and bac, and serotype V with alp3. The associations between serotype Ia and bca, bca repetitive unit, and bca repetitive unit-like sequence-containing genes need to be studied further. These PCR-based methods will provide an alternative and objective tool for subtyping of GBS based on surface protein antigen genes.
| S-EPMC153396 | biostudies-literature
Project description:BackgroundGroup B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates.MethodsWe conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0-89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence.ResultsWe identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43-.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36-.47); late-onset disease incidence was 0.26 (95% CI, .21-.30). CFR was 8.4% (95% CI, 6.6%-10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V.ConclusionsThe incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.
| S-EPMC5850457 | biostudies-literature
Project description:This study aimed to evaluate the potential of oral probiotics to eradicate vaginal GBS colonization during the third trimester of pregnancy. We screened 1058 women for GBS colonization at 33-37 gestational weeks using a combination of vaginal-to-rectal swab and culture-based methods. Women who tested GBS positive were randomized to either the verum group, receiving a dietary probiotic supplement of four viable strains of Lactobacillus twice-daily for 14 days, or to the placebo group. Women underwent follow-up smears, whereat GBS colonization upon follow-up was considered the primary endpoint. We found that 215 women (20.3%) were positive for GBS upon screening, of which 82 (38.1%) were eligible for study inclusion; 41 (50%) of these were randomized to the verum and placebo groups each. After treatment, 21/33 (63.6%) members of the verum group, and 21/27 (77.8%) of the placebo group were still GBS positive (p?=?0.24). Four (9.8%) women in the verum group and one (2.4%) in the placebo group experienced preterm birth (p?=?0.20); smokers showed significantly higher rates of preterm birth (p?=?0.03). Hence, the findings did not support the hypothesis that oral probiotics can eradicate GBS during pregnancy, although we observed a trend toward reduced GBS persistence after probiotic intake.
| S-EPMC7665007 | biostudies-literature
Project description:Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 "latching" domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr-fibrinogen interactions in the female reproductive tract.
| S-EPMC4192050 | biostudies-literature