scholarly journals Structure ofStreptococcus agalactiaeglyceraldehyde-3-phosphate dehydrogenase holoenzyme reveals a novel surface

2014 ◽  
Vol 70 (10) ◽  
pp. 1333-1339 ◽  
Author(s):  
Chapelle A. Ayres ◽  
Norbert Schormann ◽  
Olga Senkovich ◽  
Alexandra Fry ◽  
Surajit Banerjee ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Group B Streptococcus ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Significant Difference ◽  
Potential Vaccine ◽  
Group B

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a conserved cytosolic enzyme, which plays a key role in glycolysis. GAPDH catalyzes the oxidative phosphorylation of D-glyceraldehyde 3-phosphate using NAD or NADP as a cofactor. In addition, GAPDH localized on the surface of some bacteria is thought to be involved in macromolecular interactions and bacterial pathogenesis. GAPDH on the surface of group B streptococcus (GBS) enhances bacterial virulence and is a potential vaccine candidate. Here, the crystal structure of GBS GAPDH fromStreptococcus agalactiaein complex with NAD is reported at 2.46 Å resolution. Although the overall structure of GBS GAPDH is very similar to those of other GAPDHs, the crystal structure reveals a significant difference in the area spanning residues 294–307, which appears to be more acidic. The amino-acid sequence of this region of GBS GAPDH is also distinct compared with other GAPDHs. This region therefore may be of interest as an immunogen for vaccine development.

scholarly journals Evaluation of Recombinant Lipidated P2086 Protein as a Vaccine Candidate for Group B Neisseria meningitidis in a Murine Nasal Challenge Model

2005 ◽  
Vol 73 (10) ◽  
pp. 6838-6845 ◽  
Author(s):  
Duzhang Zhu ◽  
Ying Zhang ◽  
Vicki Barniak ◽  
Liesel Bernfield ◽  
Alan Howell ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Active Immunization ◽  
Human Beings ◽  
Nasal Tissue ◽  
Potential Vaccine ◽  
Group B ◽  
Different Strains

ABSTRACT Neisseria meningitidis is a major causative agent of bacterial meningitis in human beings, especially among young children (≤2 years of age). Prevention of group B meningococcal disease represents a particularly difficult challenge in vaccine development, due to the inadequate immune response elicited against type B capsular polysaccharide. We have established an adult mouse intranasal challenge model for group B N. meningitidis to evaluate potential vaccine candidates through active immunization. Swiss Webster mice were inoculated intranasally with meningococci, and bacteria were recovered from the noses for at least 3 days postchallenge. Iron dextran was required in the bacterial inoculum to ensure sufficient meningococcal recovery from nasal tissue postchallenge. This model has been utilized to evaluate the potential of a recombinant lipidated group B meningococcal outer membrane protein P2086 (rLP2086) as a vaccine candidate. In this study, mice were immunized subcutaneously with purified rLP2086 formulated with or without an attenuated cholera toxin as an adjuvant. The mice were then challenged intranasally with N. meningitidis strain H355 or M982, and the colonization of nasal tissue was determined by quantitative culture 24 h postchallenge. We demonstrated that immunization with rLP2086 significantly reduced nasal colonization of mice challenged with the two different strains of group B N. meningitidis. Mice immunized with rLP2086 produced a strong systemic immunoglobulin G response, and the serum antibodies were cross-reactive with heterologous strains of group B N. meningitidis. The antibodies have functional activity against heterologous N. meningitidis strain, as demonstrated via bactericidal and infant rat protection assays. These results suggest that rLP2086 is a potential vaccine candidate for group B N. meningitidis.

scholarly journals Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maricarmen Rojas-Lopez ◽  
Manuele Martinelli ◽  
Valentina Brandi ◽  
Grégory Jubelin ◽  
Fabio Polticelli ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Bacterial Load ◽  
Enterohemorrhagic Escherichia Coli ◽  
Protein Antigens ◽  
E Coli ◽  
Epidemiology Data ◽  
Potential Vaccine

AbstractEnterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.

scholarly journals Antenatal Screening for Group B Streptococcus in the Setting of Preterm Premature Rupture of Membranes: Empiric versus Culture-based Prophylaxis

2020 ◽  
Vol 10 (01) ◽  
pp. e26-e31
Author(s):  
Leena B. Mithal ◽  
Nirali Shah ◽  
Anna Romanova ◽  
Emily S. Miller
Keyword(s):  
Multivariable Analysis ◽  
Group B Streptococcus ◽  
Preterm Neonates ◽  
Premature Rupture Of Membranes ◽  
Premature Rupture ◽  
Preterm Premature Rupture ◽  
Significant Difference ◽  
Culture Sensitivity ◽  
Intrapartum Antibiotic ◽  
Group B

Abstract Objective Imperfect culture sensitivity and increase of early onset neonatal sepsis (EONS) risk in preterm neonates raise concern that culture-based intrapartum antibiotic prophylaxis (IAP) may be insufficient after preterm premature rupture of membranes (PPROM). Our objective was to compare rates of EONS after empiric versus culture-based IAP in PPROM. Study Design This retrospective cohort study included women with a singleton gestation and PPROM between 23 and 33 weeks. Outcomes after culture-based IAP were compared with empiric IAP. The primary outcome was EONS. Secondary outcomes included group B streptococcus (GBS) bacteremia, bacteremia, and neonatal GBS infection. Bivariable and multivariable logistic analyses were performed. Results Of the 270 women who met inclusion criteria, 136 (50%) had culture-based IAP of whom 36 (26.5%) were GBS positive. There was no significant difference in bacteremia (2.2 vs. 4.5%, p = 0.30), GBS infection (0.8 vs. 0.7%, p = 1.00), or EONS (11.8 vs. 12.7%, p = 0.82) in infants of women with culture-based IAP compared with empiric IAP. Multivariable analysis confirmed a lack of advantage to empiric versus culture-based IAP in EONS risk (adjusted odds ratio [aOR] = 0.82, 95% confidence interval [CI]: 0.44–1.93). Conclusion In pregnancies complicated by PPROM, infants of women who received culture-based IAP had no significant difference in EONS or GBS infection compared with infants of women with empiric IAP.

scholarly journals Serotype Distribution, Population Structure, and Antimicrobial Resistance of Group B Streptococcus Strains Recovered from Colonized Pregnant Women

2016 ◽  
Vol 55 (2) ◽  
pp. 412-422 ◽  
Author(s):  
Sarah Teatero ◽  
Patricia Ferrieri ◽  
Irene Martin ◽  
Walter Demczuk ◽  
Allison McGeer ◽  
...  
Keyword(s):  
Population Structure ◽  
Pregnant Women ◽  
Antimicrobial Agents ◽  
Vaccine Development ◽  
Group B Streptococcus ◽  
Tetracycline Resistance ◽  
The United States ◽  
High Rate ◽  
Content Type ◽  
Group B

ABSTRACTUsing serotyping, multilocus sequence typing, and whole-genome sequencing (WGS) of selected strains, we studied the population structure of 102 group BStreptococcus(GBS) isolates prospectively sampled in 2014 from vaginal/rectal swabs of healthy pregnant women in metropolitan Toronto, Canada. We also determined the susceptibilities of each of the colonizing isolates to penicillin, erythromycin, clindamycin, tetracycline, and other antimicrobial agents. Overall, we observed a high rate of tetracycline resistance (89%) among colonizing GBS isolates. We found resistance to erythromycin in 36% of the strains, and 33% were constitutively or inducibly resistant to clindamycin. The most frequently identified serotypes were III (25%), Ia (23%), and V (19%). Serotype IV accounted for 6% of the colonizing isolates, a rate consistent with that observed among patients with invasive GBS infections in metropolitan Toronto. The majority of serotype IV isolates belonged to sequence type (ST)459, a tetracycline-, erythromycin-, and clindamycin-resistant ST first identified in Minnesota, which is considered to be the main driver of serotype IV GBS expansion in North America. WGS revealed that ST459 isolates from Canada are clonally related to colonizing and invasive ST459 organisms circulating in regions of the United States. We also used WGS to study recombination in selected colonizing strains from metropolitan Toronto, which revealed multiple episodes of capsular switching. Present and future circulating GBS organisms and their genetic diversity may influence GBS vaccine development.

scholarly journals High cephalosporin resistance due to amino acid substitutions in PBP1A and PBP2X in a clinical isolate of group B Streptococcus

2013 ◽  
Vol 68 (7) ◽  
pp. 1533-1536 ◽  
Author(s):  
Kouji Kimura ◽  
Jun-ichi Wachino ◽  
Hiroshi Kurokawa ◽  
Mari Matsui ◽  
Satowa Suzuki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Clinical Isolate ◽  
Group B Streptococcus ◽  
Amino Acid Substitutions ◽  
Cephalosporin Resistance ◽  
Group B

scholarly journals Temporal Changes in Invasive Group B Streptococcus Serotypes: Implications for Vaccine Development

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0169101 ◽  
Author(s):  
Ziyaad Dangor ◽  
Clare L. Cutland ◽  
Alane Izu ◽  
Gaurav Kwatra ◽  
Siobhan Trenor ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Group B Streptococcus ◽  
Temporal Changes ◽  
Invasive Group ◽  
Group B

scholarly journals Molecular epidemiology of infections caused by group B Streptococcus in pregnant women and newborns, and development of preventive vaccines

2018 ◽  
Vol 67 (5) ◽  
pp. 62-73
Author(s):  
Vasilisa A. Vasilyeva ◽  
Elena V. Shipitsyna ◽  
Kira V. Shalepo ◽  
Alevtina M. Savicheva
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Group B Streptococcus ◽  
Epidemiological Data ◽  
Group B Streptococci ◽  
Group B ◽  
Sequence Types ◽  
Experimental Immunization ◽  
Selection Of

Hypothesis/aims of study. The present analysis was undertaken to summarize current knowledge about molecular properties of group B streptococci (GBS), emphasizing potential targets of vaccines against neonatal GBS infection. Study design, materials, and methods. This review is based on articles published mainly in the last ten years. Results. Epidemiological data on serotypes, multilocus sequence types, clonal complexes of GBS and their relationship are presented. Genetic events in GBS populations indicate significant obstacles to vaccine development. We described key properties of major GBS virulence factors, such as capsular polysaccharide, pili, and cell adhesion molecules, as well as results of experimental immunization on their basis. Conclusion. The population of invasive GBS strains is molecularly and genetically heterogeneous, which complicates selection of vaccine targets. Capsular switching, a low level of immunogenicity and variability of population composition are the most important factors that necessitate the accumulation and monitoring of molecular epidemiological data.

scholarly journals Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2355 ◽  
Author(s):  
Miwako Kobayashi ◽  
Johan Vekemans ◽  
Carol J. Baker ◽  
Adam J. Ratner ◽  
Kirsty Le Doare ◽  
...  
Keyword(s):  
At Risk ◽  
Disease Burden ◽  
Vaccine Development ◽  
Young Infant ◽  
Group B Streptococcus ◽  
Current Status ◽  
Middle Income ◽  
Young Infants ◽  
Group B ◽  
Low And Middle Income

Globally, group BStreptococcus(GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation.This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations.

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