ArticleMolecular microbiology2010
Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract.
Article in Molecular microbiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 83 citations in OpenAlex.
- Group A Streptococcus secreted esterase hydrolyzes platelet-activating factor to impede neutrophil recruitment and facilitate innate immune evasion.PLoS pathogens · 2012Trial
- SpyCEP dismantles neutrophil immunity via disorder-driven chemokine remodeling and GAG targeting.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rational selection of antigenic targets for Group A Streptococcus vaccine: updates, challenges and opportunities.NPJ vaccines · 2026Review
- Discerning dangerous gain of function: most gain of function (GoF) research does not involve infectious microbes.Frontiers in bioengineering and biotechnology · 2026Review
- TheJournal of bacteriology · 2025Article
- Annotation of Functions of Sequences of Concern and Its Relevance to the New Biosecurity Regulatory Framework in the United States.Applied biosafety : journal of the American Biological Safety Association · 2024Article
- Immunomodulating Enzymes fromMicroorganisms · 2024Review
- Structure-activity studies of Streptococcus pyogenes enzyme SpyCEP reveal high affinity for CXCL8 in the SpyCEP C-terminal.Scientific reports · 2023Article
- Review
- Streptococcal peptides and their roles in host-microbe interactions.Frontiers in cellular and infection microbiology · 2023Review
- Article
- The group AInfectious microbes & diseases · 2022Article
- Categorizing Sequences of Concern by Function To Better Assess Mechanisms of Microbial Pathogenesis.Infection and immunity · 2022Review
- Secretory Proteases of the Human Skin Microbiome.Infection and immunity · 2022Article
- Function-based classification of hazardous biological sequences: Demonstration of a new paradigm for biohazard assessments.Frontiers in bioengineering and biotechnology · 2022Article
- The Role of Streptococcal Cell-Envelope Proteases in Bacterial Evasion of the Innate Immune System.Journal of innate immunity · 2022Review
- Multicomponent Vaccines against Group A Streptococcus Can Effectively Target Broad Disease Presentations.Vaccines · 2021Article
- Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease.NPJ vaccines · 2021Article
- Neutrophil recruitment by chemokines Cxcl1/KC and Cxcl2/MIP2: Role of Cxcr2 activation and glycosaminoglycan interactions.Journal of leukocyte biology · 2021Article
- Intracellular Group AmBio · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
SpyCEP is a Streptococcus pyogenes protease that cleaves CXCL8/IL-8 and its activity is associated with human invasive disease severity. We investigated the role of SpyCEP in S. pyogenes necrotizing fasciitis and respiratory tract infection in mice using isogenic strains differing only in SpyCEP expression. SpyCEP cleaved human CXCL1, 2, 6 and 8 plus murine CXCL1 and 2 at a structurally conserved site. Mice were infected in thigh muscle with a strain of S. pyogenes that expresses a high level of SpyCEP, or with an isogenic non-SpyCEP expressing strain. SpyCEP expression by S. pyogenes hindered bacterial clearance from muscle, and enhanced bacterial spread, associated with cleavage of murine chemoattractant CXCL1. Mice were then infected with Lactococcus lactis strains that differed only in SpyCEP expression. In contrast to the parent L. lactis strain (lacks SpyCEP), which was avirulent when administered intramuscularly, infection with a strain that expressed SpyCEP heterologously led to dramatic systemic illness within 24 h, failure to clear bacteria from muscle and marked dissemination to other organs. In the upper airways, SpyCEP expression was required for survival of L. lactis but not S. pyogenes. However, dissemination of S. pyogenes to the lung was SpyCEP-dependent and was associated with evidence of chemokine cleavage. Taken together, the studies provide clear evidence that SpyCEP is necessary and sufficient for systemic bacterial dissemination from a soft tissue focus in this model and also underlies dissemination in the respiratory tract.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.