ArticlePloS one2009
Functional dissection of Streptococcus pyogenes M5 protein: the hypervariable region is essential for virulence.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Role of serotype and virulence determinants ofFrontiers in cellular and infection microbiology · 2023Article
- Streptococcus pyogenes Forms Serotype- and Local Environment-Dependent Interspecies Protein Complexes.mSystems · 2021Article
- Subdominance in Antibody Responses: Implications for Vaccine Development.Microbiology and molecular biology reviews : MMBR · 2020Review
- A quantitative Streptococcus pyogenes-human protein-protein interaction map reveals localization of opsonizing antibodies.Nature communications · 2019Article
- Variation, Indispensability, and Masking in the M protein.Trends in microbiology · 2018Review
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- Variable region in streptococcal M-proteins provides stable binding with host fibrinogen for plasminogen-mediated bacterial invasion.The Journal of biological chemistry · 2017Article
- Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.MicrobiologyOpen · 2015Article
- A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.The Journal of infectious diseases · 2014Article
- Article
- Article
- Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence.PLoS pathogens · 2013Article
- Protective activity of Streptococcus pneumoniae Spr1875 protein fragments identified using a phage displayed genomic library.PloS one · 2012Article
- Bacterial plasminogen receptors utilize host plasminogen system for effective invasion and dissemination.Journal of biomedicine & biotechnology · 2012Review
- The nonideal coiled coil of M protein and its multifarious functions in pathogenesis.Advances in experimental medicine and biology · 2011Review
- The NH(2)-terminal region of Streptococcus pyogenes M5 protein confers protection against degradation by proteases and enhances mucosal colonization of mice.The Journal of infectious diseases · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M5 is required for mouse virulence and binds mouse and human Fg equally well, as shown here. Mixed infection experiments with wild type bacteria demonstrated that mutants lacking the N-terminal hypervariable region (HVR) or the Fg-binding B-repeat region were strongly attenuated, while a mutant lacking the conserved C-repeats was only slightly attenuated. Because the HVR of M5 is not required for phagocytosis resistance, our data imply that this HVR plays a major but unknown role during acute infection. The B-repeat region is required for phagocytosis resistance and specifically binds Fg, suggesting that it promotes virulence by binding Fg. However, B-repeat mutants were attenuated even in Fg-deficient mice, implying that the B-repeats may have a second function, in addition to Fg-binding. These data demonstrate that two distinct M5 regions, including the HVR, are essential to virulence during the early stages of an infection. In particular, our data provide the first in vivo evidence that the HVR of an M protein plays a major role in virulence, focusing interest on the molecular role of this region.
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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.