Semi-Synthetic Vaccines Composed of Capsular Polysaccharides of Pathogenic Bacteria Covalently Bound to Proteins for the Prevention of Invasive Diseases

2015 ◽  
pp. 144-158
Author(s):  
Rachel Schneerson ◽  
John E. Robbins ◽  
Chiayung Chu ◽  
Ann Sutton ◽  
Gerald Schiffman ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Capsular Polysaccharides ◽  
Synthetic Vaccines ◽  
Invasive Diseases ◽  
Covalently Bound

scholarly journals A Structural Model for the Ligand Binding of Pneumococcal Serotype 3 Capsular Polysaccharide-Specific Protective Antibodies

mBio ◽  
2021 ◽  
Author(s):  
Ahmet Ozdilek ◽  
Jiachen Huang ◽  
Rachelle Babb ◽  
Amy V. Paschall ◽  
Dustin R. Middleton ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Structural Model ◽  
Capsular Polysaccharide ◽  
Capsular Polysaccharides ◽  
Bacterial Diseases ◽  
Major Threat ◽  
Protective Antibodies ◽  
Pneumococcal Serotype ◽  
Glycoconjugate Vaccines ◽  
Main Components

Infectious diseases caused by pathogenic bacteria are a major threat to human health. Capsular polysaccharides (CPSs) of many pathogenic bacteria have been used as the main components of glycoconjugate vaccines against bacterial diseases in clinical practice worldwide, with various degrees of success.

scholarly journals Effects of galU Mutation on Pseudomonas syringae–Plant Interactions

2010 ◽  
Vol 23 (9) ◽  
pp. 1184-1196 ◽  
Author(s):  
Wen-Ling Deng ◽  
Yuan-Chun Lin ◽  
Rong-Hwa Lin ◽  
Chia-Fong Wei ◽  
Yi-Chiao Huang ◽  
...  
Keyword(s):  
Pseudomonas Syringae ◽  
Type Iii Secretion ◽  
Pathogenic Bacteria ◽  
Capsular Polysaccharides ◽  
Uridine Diphosphate ◽  
Plant Interactions ◽  
In Planta ◽  
Animal Pathogens ◽  
Diphosphate Glucose ◽  
Molecular Patterns

Bacterial galU coding for a uridine diphosphate-glucose pyrophosphorylase plays an important role in carbohydrates biosynthesis, including synthesis of lipopolysaccharides (LPS), membrane-derived oligosaccharides, and capsular polysaccharides. In this study, we characterized the galU mutant of Pseudomonas syringae pv. syringae 61 (Psy61), a necrotizing plant pathogen whose pathogenicity depends on a functional type III secretion system (T3SS), and showed that the Psy61 galU mutant had reduced biofilm formation ability, was nonmotile, and had an assembled T3SS structure but failed to elicit hypersensitive response in resistant plants and necrotic lesions in susceptible plants. Moreover, the defective LPS and other pathogen-associated molecular patterns (PAMPs) on the surface of the Psy61 galU mutant were capable of inducing PAMP-triggered immunity, which severely compromised the ability of the Psy61 galU mutant to survive in planta. Our results demonstrated that the complete LPS protected plant-pathogenic bacteria from host innate immunity, similar to what was found in animal pathogens, prior to the translocation of T3S effectors and bacterial multiplication.

scholarly journals Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

2021 ◽  
Vol 17 ◽  
pp. 2915-2921
Author(s):  
Tanmoy Halder ◽  
Somnath Yadav
Keyword(s):  
Total Synthesis ◽  
Pathogenic Bacteria ◽  
Capsular Polysaccharides ◽  
One Pot ◽  
Antibiotic Resistant ◽  
O Antigen ◽  
The Family ◽  
Providencia Stuartii ◽  
The One ◽  
Tract Infections

Capsular polysaccharides of pathogenic bacteria have been reported to be effective vaccines against diseases caused by them. Providencia stuartii is a class of enterobacteria of the family Providencia that is responsible for several antibiotic resistant infections, particularly urinary tract infections of patients with prolonged catheterization in hospital settings. Towards the goal of development of vaccine candidates against this pathogen, we herein report the total synthesis of a trisaccharide repeating unit of the O-antigen polysaccharide of the P. stuartii O49 serotype containing the →6)-β-ᴅ-Galp-(1→3)-β-ᴅ-GalpNAc(1→4)-α-ᴅ-Galp(1→ linkage. The synthesis of the trisaccharide repeating unit was carried out first by a linear strategy involving the [1 + (1 + 1 = 2)] assembly, followed by a one-pot synthesis involving [1 + 1 + 1] strategy from the corresponding monosaccharides. The one-pot method provided a higher yield of the protected trisaccharide intermediate (73%) compared to the two step synthesis (66%). The protected trisaccharide was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside.

scholarly journals Avidity as a Determinant of the Protective Efficacy of Human Antibodies to Pneumococcal Capsular Polysaccharides

1999 ◽  
Vol 67 (5) ◽  
pp. 2366-2370 ◽  
Author(s):  
William R. Usinger ◽  
Alexander H. Lucas
Keyword(s):  
Capsular Polysaccharide ◽  
Important Determinant ◽  
Protective Efficacy ◽  
Inverse Correlation ◽  
Capsular Polysaccharides ◽  
Human Antibodies ◽  
Invasive Diseases ◽  
20 Nm ◽  
The Relationship

ABSTRACT Antibodies reactive with capsular polysaccharides are considered the principal mediators of immunity against invasive diseases caused byStreptococcus pneumoniae. In this study, we tested the hypothesis that anti-pneumococcal capsular polysaccharide (PPS) antibody avidity can influence protective efficacy. We measured the avidities of individual adult postvaccination immunoglobulin G2 (IgG2) antibodies to PPS serotypes 6B and 23F and examined the relationship between avidity and opsonophagocytic and mouse-protective activities. The avidities of PPS 6B- and PPS 23F-specific IgG2 antibodies ranged from 6 to 31 nM−1 and from 3 to 20 nM−1, respectively. We observed an inverse correlation between the magnitude of avidity and the amount of antibody required to protect mice against lethal bacteremia caused by serotype 6B pneumococci. Similarly, higher-avidity antibodies were more effective than lower-avidity antibodies in vitro in mediating complement-dependent opsonophagocytosis of both 6B and 23F pneumococci. These data suggest that in adults, PPS antibodies are sufficiently polymorphic to possess biologically significant variations in avidity. We conclude that avidity functions as an important determinant of anticapsular antibody protective efficacy against pneumococci.

On conditionally pathogenic microflora of caspian seal ( Phoca caspica)

2015 ◽  
Vol 182 (3) ◽  
pp. 213-219
Author(s):  
Victoria V. Volodina ◽  
Svetlana A. D’Jakova ◽  
Ekaterina Ruban ◽  
Dina I. Shokasheva
Keyword(s):  
Pathogenic Bacteria ◽  
Physiological State ◽  
Anthropogenic Pollution ◽  
Pathogenic Microorganisms ◽  
The Caspian Sea ◽  
Invasive Diseases ◽  
Epidemiological Risk ◽  
Microbial Associations ◽  
Combined Infection ◽  
Caspian Seal

Caspian seal was subjected in the 2000s to complex combined infection caused by viruses and pathogenic bacteria that led to mass mortality of this species, the only marine mammal in the Caspian Sea. So, bacteriological monitoring and detection of pathogenic microorganisms in internals and tissues of the seal were conducted in the 2007-2014 and a broad spectrum of high-adaptive pathogenic microbial associations was found. The examined mammals had not diseases of bacterial origin in that time, and the most part of this microflora was qualified as the resident one, but these bacteria were able to trigger infectious process in case of deterioration of environmental conditions (anthropogenic pollution, malnutrition, lack of ice fields, etc.). Composition and abundance of the conditionally pathogenic microflora depended on physiological state of seals: the animals with invasive diseases had more abundant and diverse sanitary-indicative microorganisms. Presence of highly adaptive opportunistic microorganisms in the organism of seal is a sign of unfavourable sanitary-microbiological state of this species and considerable persistence of sanitary-indicative microflora in the ecosystem of the Volga-Caspian basin, with significant parasitizing and multiple antibiotic resistance, that is a background for high epidemiological risk.

scholarly journals Capsular Polysaccharide Is a Receptor of a Clostridium perfringens Bacteriophage CPS1

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1002 ◽  
Author(s):  
Eunsu Ha ◽  
Jihwan Chun ◽  
Minsik Kim ◽  
Sangryeol Ryu
Keyword(s):  
Clostridium Perfringens ◽  
Pathogenic Bacteria ◽  
Capsular Polysaccharide ◽  
Capsular Polysaccharides ◽  
Foodborne Illnesses ◽  
Gene Encoding ◽  
Antibiotic Resistant ◽  
Common Causes ◽  
Biochemical Analyses ◽  
Tn5 Mutant

Clostridium perfringens is a Gram-positive, anaerobic, and spore forming bacterium that is widely distributed in the environment and one of the most common causes of foodborne illnesses. Bacteriophages are regarded as one of the most promising alternatives to antibiotics in controlling antibiotic-resistant pathogenic bacteria. Here we isolated a virulent C. perfringens phage, CPS1, and analysis of its whole genome and morphology revealed a small genome (19 kbps) and a short noncontractile tail, suggesting that CPS1 can be classified as a member of Picovirinae, a subfamily of Podoviridae. To determine the host receptor of CPS1, the EZ-Tn5 random transposon mutant library of C. perfringens ATCC 13124 was constructed and screened for resistance to CPS1 infection. Analysis of the CPS1-resistant mutants revealed that the CPF_0486 was disrupted by Tn5. The CPF_0486 was annotated as galE, a gene encoding UDP-glucose 4-epimerase (GalE). However, biochemical analyses demonstrated that the encoded protein possessed dual activities of GalE and UDP-N-acetylglucosamine 4-epimerase (Gne). We found that the CPF_0486::Tn5 mutant produced a reduced amount of capsular polysaccharides (CPS) compared with the wild type. We also discovered that glucosamine and galactosamine could competitively inhibit host adsorption of CPS1. These results suggest that CPS acts as a receptor for this phage.

scholarly journals Neonatal administration of idiotype or antiidiotype primes for protection against Escherichia coli K13 infection in mice.

1984 ◽  
Vol 160 (4) ◽  
pp. 1001-1011 ◽  
Author(s):  
K E Stein ◽  
T Söderström
Keyword(s):  
Pathogenic Bacteria ◽  
Antibody Responses ◽  
Dual Function ◽  
Capsular Polysaccharides ◽  
Microbial Infection ◽  
Passive Protection ◽  
E Coli ◽  
Protective Antibodies ◽  
Live Bacteria ◽  
Neonatal Administration

Antibodies directed against the capsular polysaccharides (Ps) of encapsulated pathogenic bacteria can protect the host against infection with such organisms. The immune response to Ps, however, does not develop until relatively late in ontogeny. We have, therefore, studied alternative ways to stimulate anti-Ps antibody responses in neonates, namely priming with idiotype (Id) and anti-Id. We believe that these studies provide the first demonstration of the use of an anti-Id antibody to prime for protection against a bacterial infection and the first demonstration of the ability of a monoclonal anti-Id to prime for protection against any microbial infection. We have used a monoclonal IgM Id, anti-K13 capsular antibody, and a monoclonal IgG1 anti-Id in studies of the effects of administration of anti-Id or Id within 24 h after birth on the ability of mice to respond to subsequent immunization and challenge with live bacteria. These studies show that neonatal administration of 1 micrograms of Id or 50 ng of anti-Id lead to significantly enhanced protection in mice immunized at 4 wk of age and challenged at 5 wk with an intraperitoneal injection of 20-30 LD50 of E. coli 06:K13:H1, as compared with unprimed or antigen (Ps)-primed controls. Mice primed at birth, immunized at 12 wk of age, a time when they can respond fully to Ps itself, and challenged 1 wk later, were still significantly protected by anti-Id priming but no longer showed the effects of Id. We conclude that administration of protective Id early in life may serve a dual function in providing immediate passive protection as well as priming for protective antibodies upon subsequent antigen exposure.

scholarly journals Genotyping and Phylogenetic Analysis of Group B Streptococcus by Multiple Locus Variable Number Tandem Repeat Analysis in Iran

2018 ◽  
Vol 7 ◽  
pp. e1121
Author(s):  
Farzaneh Khodaei ◽  
Behrooz Sadeghi Kalani ◽  
Naser Alizadeh ◽  
Alka Hassani ◽  
Mohammad Najafi ◽  
...  
Keyword(s):  
Tandem Repeat ◽  
Group B Streptococcus ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Capsular Polysaccharides ◽  
Multiple Locus ◽  
Repeat Analysis ◽  
Invasive Diseases ◽  
Group B ◽  
Relationship Of

Background: Group B streptococcus (GBS), also known as Streptococcus agalactiae, is well known as a causative agent for neonatal invasive diseases; it is also a major pathogen in adults. Analytic epidemiology is required to monitor the clinical isolates of GBS. However, there is insufficient information on the genetic background of GBS in Iran, and this information is needed to guide and develop a GBS vaccine. Materials and Methods: In total, 90 well-characterized GBS isolates were collected from April 2014 to August 2015. In this study, molecular typing was used to disclose a relationship between the multiple-locus variable number tandem repeat analysis (MLVA) types, serotyping, and pilus islands. The isolates were characterized by the types of capsular polysaccharides and pilus islands and were examined by MLVA to study the epidemiological relationship of isolates. Results: The results indicate that there is a significant relationship between the distribution of serotypes and pilus island genes; GBS isolates were differentiated into 12 types by capsular polysaccharides and pilus islands analysis. The discriminatory power of an MLVA analysis was high based on the five most variable numbers of tandem repeat loci and 44 MLVA types that were identified. Conclusions: This study has provided useful insights into the genetic heterogeneity of GBS isolates in Tehran and Alborz, Iran. The extensive distribution of pilus islands in various serotypes and MLVA types throughout the GBS population refers to the advancement of the pilus-based GBS vaccines. [GMJ.2018;7:e1121]

Capsules of Escherichia coli, expression and biological significance

1992 ◽  
Vol 38 (7) ◽  
pp. 705-710 ◽  
Author(s):  
Klaus Jann ◽  
Barbara Jann
Keyword(s):  
Escherichia Coli ◽  
Host Defense ◽  
Pathogenic Bacteria ◽  
Biological Significance ◽  
Surface Expression ◽  
Capsular Polysaccharides ◽  
Virulence Determinants ◽  
E Coli ◽  
Group I ◽  
Group Ii

Escherichia coli may cause intestinal or extraintestinal infections. Generally, extraintestinal E. coli are encapsulated. The capsules are important virulence determinants, which enable the pathogenic bacteria to evade or counteract the unspecific host defense during the early (preimmune) phase of infection. They interfere with the action of complement and phagocytes. This effect is generally transient and overcome by capsule-specific antibodies in the immune phase of the host defense. In some cases, capsules are not or only poorly immunogenic, as a result of structural relationship or identity with host material. Strains with such capsules (e.g., K1 or K5) are very virulent. Bacterial capsules consist of acidic polysaccharides, which are made up from oligosaccharide repeating units. The capsules of E. coli are divided into two groups, which differ in chemistry, biochemistry, and genetic organization. All capsular polysaccharides are chromosomally determined: those of group I close to his and those of group II close to serA. The biosynthesis and surface expression have been extensively studied with representatives of group II capsular polysaccharides. It could be shown that their biosynthesis is directed from a gene block that determines the synthesis of the polysaccharide, its translocation across the cytoplasmic membrane, as well as its surface expression in a coordinate process. The chemical nature of group II capsular polysaccharides, as well as the mechanism(s) of their biosynthesis and expression, is presented. Key words: Escherichia coli, capsular polysaccharides, structure, genetics, biology.

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