Lipid Peptide Core Nanoparticles as Multivalent Vaccine Candidates against Streptococcus pyogenes

2012 ◽  
Vol 65 (1) ◽  
pp. 35 ◽  
Author(s):  
Mariusz Skwarczynski ◽  
Bibi Hamideh Parhiz ◽  
Fatemeh Soltani ◽  
Saranya Srinivasan ◽  
Khairul A. Kamaruzaman ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Subunit Vaccine ◽  
Click Reaction ◽  
Group A Streptococcus ◽  
Vaccine Candidates ◽  
Wide Range ◽  
Group A ◽  
Core Peptide ◽  
Aqueous Conditions ◽  
Peptide Core

Traditional vaccine approaches for Group A streptococcus (GAS) infection are inadequate owing to the host’s production of cross-reactive antibodies that recognize not only the bacteria but also human tissue. To overcome this problem a peptide subunit-based vaccine was proposed, which would incorporate only minimal non-cross reactive epitopes. However, special delivery systems/adjuvants were required because short peptides are not immunogenic. In this study we have incorporated two epitopes from two different GAS proteins into a lipid core peptide (LCP) self-adjuvanting delivery system to achieve better protection against a wide range of GAS serotypes. Multivalent and monovalent constructs were synthesized with the help of an azide alkyne cycloaddition (click) reaction and their ability to self-assemble under aqueous conditions was examined. The compounds significantly differed in their ability to form small size nanoparticles, which are believed to be most appropriate for peptide-based subunit vaccine delivery. The LCP conjugates possessing two different epitopes, in contrast to monoepitopic constructs, formed small nanoparticles (5–15 nm) presumably owing to a suitable hydrophilic-hydrophobic balance of the molecules.

Structure–activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates

2016 ◽  
Vol 24 (14) ◽  
pp. 3095-3101 ◽  
Author(s):  
Amy Chan ◽  
Waleed M. Hussein ◽  
Khairunnisa Abdul Ghaffar ◽  
Nirmal Marasini ◽  
Ahmed Mostafa ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Vaccine Candidates ◽  
Lipid Core ◽  
Structure Activity ◽  
Group A ◽  
Core Peptide ◽  
Relationship Of

Structure of ScpC, a virulence protease from Streptococcus pyogenes, reveals the functional domains and maturation mechanism

2018 ◽  
Vol 475 (17) ◽  
pp. 2847-2860 ◽  
Author(s):  
Chacko Jobichen ◽  
Ying Chong Tan ◽  
Mahalakshmi Tirumuru Prabhakar ◽  
Digant Nayak ◽  
Debabrata Biswas ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Structural Rearrangement ◽  
Functional Domains ◽  
Active Site Residues ◽  
Inhibitor Complex ◽  
Wide Range ◽  
Significant Difference ◽  
Streptococcal Species ◽  
Group A

Group A Streptococcus (GAS; Streptococcus pyogenes) causes a wide range of infections, including pharyngitis, impetigo, and necrotizing fasciitis, and results in over half a million deaths annually. GAS ScpC (SpyCEP), a 180-kDa surface-exposed, subtilisin-like serine protease, acts as an essential virulence factor that helps S. pyogenes evade the innate immune response by cleaving and inactivating C-X-C chemokines. ScpC is thus a key candidate for the development of a vaccine against GAS and other pathogenic streptococcal species. Here, we report the crystal structures of full-length ScpC wild-type, the inactive mutant, and the ScpC–AEBSF inhibitor complex. We show ScpC to be a multi-domain, modular protein consisting of nine structural domains, of which the first five constitute the PR + A region required for catalytic activity. The four unique C-terminal domains of this protein are similar to collagen-binding and pilin proteins, suggesting an additional role for ScpC as an adhesin that might mediate the attachment of S. pyogenes to various host tissues. The Cat domain of ScpC is similar to subtilisin-like proteases with significant difference to dictate its specificity toward C-X-C chemokines. We further show that ScpC does not undergo structural rearrangement upon maturation. In the ScpC–inhibitor complex, the bound inhibitor breaks the hydrogen bond between active-site residues, which is essential for catalysis. Guided by our structure, we designed various epitopes and raised antibodies capable of neutralizing ScpC activity. Collectively, our results demonstrate the structure, maturation process, inhibition, and substrate recognition of GAS ScpC, and reveal the presence of functional domains at the C-terminal region.

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

scholarly journals Association between Resistance to Erythromycin and the Presence of the Fibronectin Binding Protein F1 Gene, prtF1, in Streptococcus pyogenes Isolates from German Pediatric Patients

2005 ◽  
Vol 49 (7) ◽  
pp. 2990-2993 ◽  
Author(s):  
Maria Haller ◽  
Kirsten Fluegge ◽  
Sandra Jasminder Arri ◽  
Brit Adams ◽  
Reinhard Berner
Keyword(s):  
Streptococcus Pyogenes ◽  
Pediatric Patients ◽  
Group A Streptococcus ◽  
Binding Protein ◽  
Macrolide Resistance ◽  
Group A ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding ◽  
Cell Invasiveness

ABSTRACT A total of 301 German pediatric group A streptococcus isolates were screened for the presence of macrolide resistance and the fibronectin binding protein F1 gene (prtF1) encoding an adhesin and cell invasiveness protein. The prtF1 gene was present significantly more often among macrolide-resistant isolates. The majority of these were not clonally related.

scholarly journals Biochemical and biological activity of arginine deiminase from Streptococcus pyogenes M22

2016 ◽  
Vol 94 (2) ◽  
pp. 129-137 ◽  
Author(s):  
Eleonora A. Starikova ◽  
Alexey V. Sokolov ◽  
Anna Yu. Vlasenko ◽  
Larisa A. Burova ◽  
Irina S. Freidlin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Bacterial Pathogen ◽  
Arginine Deiminase ◽  
Dependent Manner ◽  
Group A ◽  
Micro Organisms ◽  
Dose Dependent

Streptococcus pyogenes (group A Streptococcus; GAS) is an important gram-positive extracellular bacterial pathogen responsible for a number of suppurative infections. This micro-organism has developed complex virulence mechanisms to avoid the host’s defenses. We have previously reported that SDSC from GAS type M22 causes endothelial-cell dysfunction, and inhibits cell adhesion, migration, metabolism, and proliferation in a dose-dependent manner, without affecting cell viability. This work aimed to isolate and characterize a component from GAS type M22 supernatant that suppresses the proliferation of endothelial cells (EA.hy926). In the process of isolating a protein possessing antiproliferative activity we identified arginine deiminase (AD). Further study showed that this enzyme is most active at pH 6.8. Calculating Km and Vmax gave the values of 0.67 mmol·L–1 and 42 s−1, respectively. A distinctive feature of AD purified from GAS type M22 is that its optimum activity and the maximal rate of the catalytic process is close to neutral pH by comparison with enzymes from other micro-organisms. AD from GAS type M22 suppressed the proliferative activity of endothelial cells in a dose-dependent mode. At the same time, in the presence of AD, the proportion of cells in G0/G1 phase increased. When l-Arg was added at increasing concentrations to the culture medium containing AD (3 μg·mL–1), the enzyme’s capacity to inhibit cell proliferation became partially depressed. The proportion of cells in phases S/G2 increased concomitantly, although the cells did not fully recover their proliferation activity. This suggests that AD from GAS type M22 has potential for the suppression of excessive cell proliferation.

scholarly journals Analysis of virulence factors and emm typing of Streptococcus pyogenes clinical isolates.

2019 ◽  
Author(s):  
Gustavo Enck Sambrano ◽  
Gustavo P Riboldi ◽  
Keli C Reiter ◽  
Thiago Galvão da Silva Paim ◽  
Neidmar Correa Tolfo ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Streptococcus Pyogenes ◽  
Virulence Genes ◽  
Clinical Isolates ◽  
Pcr Analysis ◽  
Tissue Tropism ◽  
Factors Analysis ◽  
Wide Range ◽  
Group A ◽  
Micro Organisms

Background: Streptococcus pyogenes, a Group A streptococci (GAS), is an important human pathogen that causes a wide range of infections. Methods: Twenty five clinical isolates of S. pyogenes were submitted to an emm typing and to a Real-time PCR analysis for 23 important virulence factors. Results: Fourteen emm types were found and the emm1 type was the most prevalent. The majority of the isolates were classified as emm pattern E, followed by A-C3. No pattern D was found. Among the virulence factors, the most prevalent were SpeG, Slo, C5a-peptidase and SPNA. Phage encoded virulence genes were also found among the strains, such as mf-2, SpeJ and SpeL. Discussion: The emm1 type was the most prevalent while the 13 others M types were distributed along the strains. No tissue tropism was found on the isolates. The virulence factors analysis demonstrated that chromosomally and phage-encoded genes were found, which confers a potential for high virulent micro-organisms.

scholarly journals Analysis of virulence factors and emm typing of Streptococcus pyogenes clinical isolates.

2019 ◽  
Author(s):  
Gustavo Enck Sambrano ◽  
Gustavo P Riboldi ◽  
Keli C Reiter ◽  
Thiago Galvão da Silva Paim ◽  
Neidmar Correa Tolfo ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Streptococcus Pyogenes ◽  
Virulence Genes ◽  
Clinical Isolates ◽  
Pcr Analysis ◽  
Tissue Tropism ◽  
Factors Analysis ◽  
Wide Range ◽  
Group A ◽  
Micro Organisms

Background: Streptococcus pyogenes, a Group A streptococci (GAS), is an important human pathogen that causes a wide range of infections. Methods: Twenty five clinical isolates of S. pyogenes were submitted to an emm typing and to a Real-time PCR analysis for 23 important virulence factors. Results: Fourteen emm types were found and the emm1 type was the most prevalent. The majority of the isolates were classified as emm pattern E, followed by A-C3. No pattern D was found. Among the virulence factors, the most prevalent were SpeG, Slo, C5a-peptidase and SPNA. Phage encoded virulence genes were also found among the strains, such as mf-2, SpeJ and SpeL. Discussion: The emm1 type was the most prevalent while the 13 others M types were distributed along the strains. No tissue tropism was found on the isolates. The virulence factors analysis demonstrated that chromosomally and phage-encoded genes were found, which confers a potential for high virulent micro-organisms.

scholarly journals Host Pathways of Hemostasis that Regulate Group A Streptococcus pyogenes Pathogenicity

2020 ◽  
Vol 21 (2) ◽  
pp. 193-201
Author(s):  
Victoria A. Ploplis ◽  
Francis J. Castellino
Keyword(s):  
Streptococcus Pyogenes ◽  
Inflammatory Responses ◽  
Group A Streptococcus ◽  
Protein A ◽  
M Protein ◽  
Severe Group ◽  
Group A ◽  
Flow Through ◽  
Hallmark Feature ◽  
Major Target

A hallmark feature of severe Group A Streptococcus pyogenes (GAS) infection is dysregulated hemostasis. Hemostasis is the primary pathway for regulating blood flow through events that contribute towards clot formation and its dissolution. However, a number of studies have identified components of hemostasis in regulating survival and dissemination of GAS. Several proteins have been identified on the surface of GAS and they serve to either facilitate invasion to host distal sites or regulate inflammatory responses to the pathogen. GAS M-protein, a surface-exposed virulence factor, appears to be a major target for interactions with host hemostasis proteins. These interactions mediate biochemical events both on the surface of GAS and in the solution when M-protein is released into the surrounding environment through shedding or regulated proteolytic processes that dictate the fate of this pathogen. A thorough understanding of the mechanisms associated with these interactions could lead to novel approaches for altering the course of GAS pathogenicity.

scholarly journals Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 823 ◽  
Author(s):  
Lili Zhao ◽  
Wanli Jin ◽  
Jazmina Gonzalez Cruz ◽  
Nirmal Marasini ◽  
Zeinab G. Khalil ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Group A Streptococcus ◽  
Vaccine Delivery ◽  
Surface Charges ◽  
Subunit Vaccines ◽  
Polyelectrolyte Complexes ◽  
Humoral Immune ◽  
Anionic Polymers ◽  
Group A

Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice; PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.

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