ArticleProceedings of the National Academy of Sciences of the United States of America2000
A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin alpha 5beta 1-fibronectin-M1 protein complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 99 citations in OpenAlex.
- Interplay between group AMicrobiology and molecular biology reviews : MMBR · 2024Review
- Review
- Group A streptococci induce stronger M protein-fibronectin interaction when specific human antibodies are bound.Frontiers in microbiology · 2023Article
- Role of serotype and virulence determinants ofFrontiers in cellular and infection microbiology · 2023Article
- AssessingFrontiers in cellular and infection microbiology · 2022Article
- Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021Review
- A new perspective in sepsis treatment: could RGD-dependent integrins be novel targets?Drug discovery today · 2020Review
- An Irreversible Inhibitor to Probe the Role ofACS chemical biology · 2020Article
- Review
- Intracellular Invasion byMicrobiology spectrum · 2019Review
- A complex interplay between the extracellular matrix and the innate immune response to microbial pathogens.Immunology · 2018Review
- Knockdown of HMGN2 increases the internalization of Klebsiella pneumoniae by respiratory epithelial cells through the regulation of α5β1 integrin expression.International journal of molecular medicine · 2016Article
- Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
- The nonideal coiled coil of M protein and its multifarious functions in pathogenesis.Advances in experimental medicine and biology · 2011Review
- The role of epithelial integrin receptors in recognition of pulmonary pathogens.Journal of innate immunity · 2009Review
- Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2008Article
- Cell adhesion molecules: potential therapeutic & diagnostic implications.Molecular biotechnology · 2008Review
- The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin assembly sites in the absence of intact fibronectin.Matrix biology : journal of the International Society for Matrix Biology · 2006Article
- Streptococcal modulation of cellular invasion via TGF-beta1 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Streptococcus pyogenes can be efficiently internalized by a variety of human epithelial cells. beta-lactam antibiotics, commonly used to treat S. pyogenes infections, do not readily permeate mammalian cells. There is growing evidence that the ability of streptococci to enter host cells contributes to the frequent failure of antibiotics to eradicate the organism from infected individuals. Recent studies have suggested that host cell entry requires the formation of a complex of a bacterial fibronectin (Fn) binding protein (e.g., M1 protein or protein F1/SfbI), human Fn, and the epithelial cell Fn receptor, integrin alpha5beta1. We report here that a low molecular weight, nonpeptide antagonist of integrin alpha5beta1, SJ755, can inhibit internalization of streptococci by primary human tonsillar epithelial cells and immortalized human epithelial (A549) cells, thus increasing the extent of bacterial killing by antibiotics. SJ755 blocked Fn binding by human tonsillar epithelial and A549 cells, suggesting that integrin alpha5beta1 is the major Fn receptor expressed by both cell types. SJ755 did not affect Fn binding by purified M1 protein or M1(+) bacteria. Purified M1 protein failed to associate with integrin alpha5beta1 unless the integrin had been prebound by Fn. Also, SJ755 blocked formation of alpha5beta1-Fn-M1 complexes in vitro. These results support the previous proposal that Fn functions as a molecular bridge between M1 protein and integrin alpha5beta1. Furthermore, these results suggest that integrin antagonists may enhance the efficacy of antibiotics in treatment of S. pyogenes infections.
Indexed as
Identifiers
What OpenQuestion holds
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.