The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells

Molinari, Gabriella; Talay, Susanne R.; Valentin‐Weigand, Peter; Rohde, Manfred; Chhatwal, Gursharan S.

doi:10.1128/iai.65.4.1357-1363.1997

Cited by 241 publications

(142 citation statements)

References 31 publications

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“…This difference is not statistically significant (P ¼ 0.07), but the results could suggest that the reduced virulence of AP1(pPTF8) bacteria in control mice ( Figure 5A) is partially restored in pFn-null mice. As pFn-null mice still express cFn in all tissues and protein F1 can interact with cFn (Ozeri et al, 1996;Molinari et al, 1997), the data support the notion that cFn prevents full restoration of virulence in pFn-null mice.…”

Section: S Pyogenes Bacteria Expressing Protein F1 Are Less Virulentsupporting

confidence: 69%

Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes

Nyberg

Sakai

Cho

et al. 2004

EMBO J

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Fibronectin-binding surface proteins are found in many bacterial species. Most strains of Streptococcus pyogenes, a major human pathogen, express the fibronectin-binding protein F1, which promotes bacterial adherence to and entry into human cells. In this study, the role of fibronectin in S. pyogenes virulence was investigated by introducing the protein F1 gene in an S. pyogenes strain lacking this gene. Furthermore, transgenic mice lacking plasma fibronectin were used to examine the relative contribution of plasma and cellular fibronectin to S. pyogenes virulence. Unexpectedly, protein F1-expressing bacteria were less virulent to normal mice, and virulence was partly restored when these bacteria were used to infect mice lacking plasma fibronectin. Dissemination to the spleen of infected mice was less efficient for fibronectin-binding bacteria. These bacteria also disseminated more efficiently in mice lacking plasma fibronectin, demonstrating that plasma fibronectin bound to the bacterial surface downregulates S. pyogenes virulence by limiting bacterial spread. From an evolutionary point of view, these results suggest that reducing virulence by binding fibronectin adds selective advantages to the bacterium.

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Section: S Pyogenes Bacteria Expressing Protein F1 Are Less Virulentsupporting

confidence: 69%

Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes

Nyberg

Sakai

Cho

et al. 2004

EMBO J

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“…Interestingly, entry of S. pyogenes has been related to caveola-dependent endocytosis; indeed, it seems to be the major entry route for S. pyogenes (41). In addition, it has been shown that beads coated with the FN-binding protein Sfbl of S. pyogenes are efficiently taken up by cells (30,41). Therefore, we suggest that binding to FN might be a general mechanism for transport of FN-bound viruses, bacteria, and other ligands into cells.…”

Section: Discussionmentioning

confidence: 99%

Matrix Fibronectin Binds Gammaretrovirus and Assists in Entry: New Light on Viral Infections

Beer¹,

Pedersen

2007

J Virol

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A major entry route for the gammaretrovirus amphotropic murine leukemia virus (A-MLV) into NIH 3T3 fibroblasts is via caveola-dependent endocytosis. However, during the infection time, few viral particles can be observed intracellularly. Analyzing the dynamics of the A-MLV infection process by using total internal reflection fluorescence microscopy, we show that the majority of viruses are extracellular and bound to the fibronectin matrix. Moreover, the amounts of bound virus and of fibronectin correlated. Using confocal microscopy, nanoparticles targeted to fibronectin by a III1C-fibronectin fragment or anti-fibronectin antibody were detected intracellularly in NIH 3T3 cells; unconjugated nanoparticles neither bound to cells nor were detectable intracellularly. Furthermore, A-MLV colocalized intracellularly with the fibronectin-targeted nanoparticles, suggesting that they were taken up by the same cellular pathway. Both A-MLV entry and fibronectin turnover depend on caveolar endocytosis, and we found that inhibiting viral binding to the extracellular NIH 3T3 fibronectin-matrix dramatically reduced A-MLV infection, indeed, showing an active role of fibronectin in infection. We suggest that binding to the cellular fibronectin matrix provides a new mechanism by which viruses can enter cells.Knowledge of the role of cellular factors in retroviral entry increases our understanding of how viruses can exploit cellular features to enter host cells. Gammaretroviruses, like other enveloped viruses, are dependent on specific cellular receptors for fusion of the viral membrane with the cellular membrane; e.g., amphotropic murine leukemia virus (A-MLV) depends on the presence of the ubiquitously expressed sodium-dependent phosphate transporter Pit2 (17,29,48,50). MLV-based retroviral vectors including vectors carrying A-MLV envelope proteins are widely used in gene therapy protocols, and although retroviruses and retroviral vectors can infect a variety of dividing cell types, the efficiencies vary greatly among different cell types despite the fact that these cells all express Pit2 (48). Specifically, efficient transduction of hematopoietic cells can only be achieved when infection occurs in the presence of chymotryptic fibronectin (FN) fragments like 30/35 FN, recombinant chimeric FN fragments like CH-296 (RetroNectin) (13, 32), or shed FN (sFN) derived from NIH 3T3-based packaging cell lines (21 and C. S. Søndergaard, C. Haldrup, C. Beer, D. B. Kohn, and L. Pedersen, submitted for publication). It has been suggested that increased infection is due to concomitant binding of vectors and cells to the fibronectin fragments and that this increases the likelihood that a vector and a cell will interact compared to the situation where both vectors and cells would be in suspension (13, 31). In agreement with this hypothesis, we could recently show that gammaretroviral vectors bind to sFN from NIH 3T3 cultures (Søndergaard et al., submitted).However, the role of naturally occurring FN in viral entry is largely unknown.FN is a compo...

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“…A standard antibiotic protection assay was used for quantification of adherent GAS after 0.5 h, 1 h and 2 h (Molinari et al, 1997). Intracellular bacteria were quantified at time points 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 20 h, 24 h and 48 h p.i.…”

Section: Adherence and Invasion Assaymentioning

confidence: 99%

Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness

Klenk

Koczan

Guthke

et al. 2005

Cellular Microbiology

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SummaryThe bacterial human pathogen Streptococcus pyogenes (group A streptococci, GAS) is able to adhere to, internalize into and cross-talk on multiple levels with its host cells. To gain insight into the Fas function in pathogenesis we used Affymetrix human genome DNA-arrays to measure temporal and global transcriptional responses of HEp-2 cells infected with M49 S. pyogenes wild-type bacteria and D D D D fas X, an isogenic S. pyogenes two-component-signal-transduction system mutant. A modified stringent statistical analysis method identified a total of 86 HEp-2 cell genes as differentially transcribed upon infection over the investigated time course. Increased expression of genes encoding proteins involved in GAS host cell adherence and internalization (fibronectin, integrin-a a a a 5) was found as a common response. In contrast to earlier reports investigating other GAS serotype strains, Ras superfamily and RhoA pathways are exploited by M49 GAS, suggesting serotype specific interactions with the host cell cytoskeleton. Despite transcriptional induction, secreted IL-8 levels of D fasX mutant infected cells were below those of non-infected cells, indicating an absence of Fas expression could be important for GAS tissue colonization and long-term intracellular persistence. Oppositely, activity of the S. pyogenes Fas-system apparently promotes high adherence and internalization rates, massive cytokine gene transcription and cytokine release, host cell apoptosis via a caspase-2 activation pathway, and cytotoxicity. Thus, the S. pyogenes Fas two-component signal transduction system could be involved in local tissue destruction and general bacterial aggressiveness towards host cells.

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The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells

Cited by 241 publications

References 31 publications

Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes

Interactions with fibronectin attenuate the virulence of Streptococcus pyogenes

Matrix Fibronectin Binds Gammaretrovirus and Assists in Entry: New Light on Viral Infections

Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness

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