A 1.7 Å structure is presented for an active form of the virulence factor ScpB, the C5a peptidase from Streptococcus agalactiae. The previously reported structure of the ScpB active site mutant exhibited a large separation (~20 Å) between the catalytic His and Ser residues. Significant differences are observed in the catalytic domain between the current and mutant ScpB structures resulting with a high RMSD (4.6 Å). The fold of the active form of ScpB is nearly identical to ScpA (RMSD 0.2 Å), the C5a-peptidase from Streptococcus pyogenes. Both ScpA and ScpB have comparable activity against human C5a, indicating neither enzyme require host proteins for C5a-ase activity. These studies are a first step in resolving reported differences in the specificities of these enzymes.
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http://dx.doi.org/10.1002/prot.26625 | DOI Listing |
J Infect Dis
October 2024
Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group, Murdoch, Western Australia, Australia, 6150.
Background: Rising incidence of invasive beta-haemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated.
Methods: A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE or GBS.
Open Forum Infect Dis
June 2024
Department of Infectious Diseases, Fiona Stanley Fremantle Hospitals Group, Murdoch Western Australia, Australia.
Background: A future (Strep A) vaccine will ideally prevent a significant burden of lower limb cellulitis; however, natural immune responses to proposed vaccine antigens following an episode of cellulitis remain uncharacterized.
Methods: We enrolled 63 patients with cellulitis and 26 with invasive beta hemolytic streptococci infection, using a multiplexed assay to measure immunoglobulin G against Strep A vaccine candidate antigens, including: streptolysin O (SLO), deoxyribonuclease B (DNB), group A carbohydrate (GAC), C5a peptidase (ScpA), cell envelope proteinase (SpyCEP), and adhesion and division protein (SpyAD). Responses in the invasive cohort were used to predict the infecting etiology in the cellulitis cohort.
Cytokine
August 2024
Department of Chemical Sciences, SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Ireland. Electronic address:
C5a peptidase, also known as ScpA, is a surface associated serine protease derived from Streptococcus pyogenes and has been described as an important factor in streptococcus virulence, capable of cleaving complement components C5a, C3 and C3a. Although the interactions of ScpA with complement components is well studied, extensive screening of ScpA activity against other pro-inflammatory cytokines is lacking. Here, ScpA's ability to cleave human pro-inflammatory cytokines was tested, revealing its ability to cleave human IFNγ, IFNλ1, IFNλ2, C5, IL-37 but with significantly reduced activities.
View Article and Find Full Text PDFIn Silico Pharmacol
January 2024
TUBITAK, Marmara Research Center, Gebze, Kocaeli Türkiye.
is one of the causative agents of bovine mastitis, which has detrimental effects on animal health and the dairy industry. Despite decades of research, the requirement for effective vaccines against the disease remains unmet. The goal of this study was to create a multi-epitope vaccine using five virulence factors of .
View Article and Find Full Text PDFVaccines (Basel)
December 2023
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
Group B ( or GBS) is the leading infectious cause of neonatal mortality, causing roughly 150,000 infant deaths and stillbirths annually across the globe. Approximately 20% of pregnant women are asymptomatically colonized by GBS, which is a major risk factor for severe fetal and neonatal infections as well as preterm birth, low birth weight, and neurodevelopmental abnormalities. Current clinical interventions for GBS infection are limited to antibiotics, and no vaccine is available.
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