A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin

Kapur, Vivek; Topouzis, Stavros; Majesky, Mark W.; Li, Fulin; Hamrick, Marcie R.; Hamill, Richard J.; Patti, Joseph M.; Musser, James M.

doi:10.1006/mpat.1993.1083

Cited by 212 publications

(220 citation statements)

References 70 publications

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“…Active SpeB cleaves the host extracellular matrix (22), immunoglobulins (23,24), and complement components (16). In addition to its ability to cleave host proteins, SpeB exerts proteolytic activity toward streptococcal surface proteins (25)(26)(27).…”

Section: Gas Supernatant Induces Cleavage Of E-cadherin-culturementioning

confidence: 99%

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Sumitomo

Nakata

Higashino

et al. 2013

Journal of Biological Chemistry

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Background: Group A Streptococcus (GAS) translocates across the host epithelial barrier. Results: Streptococcal pyrogenic exotoxin B (SpeB) directly cleaves junctional proteins. Conclusion:The proteolytic efficacy of SpeB allows GAS to translocate across the epithelial barrier. Significance: SpeB-mediated dysfunction of the epithelial barrier may have important implications for not only bacterial invasion but also dissemination of other virulence factors throughout intercellular spaces.

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Section: Gas Supernatant Induces Cleavage Of E-cadherin-culturementioning

confidence: 99%

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Sumitomo

Nakata

Higashino

et al. 2013

Journal of Biological Chemistry

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“…52 Another important molecule whose RNA was present in high amounts in our tissue model was GAS cysteine protease SpeB, which has been shown to cleave many host proteins including cytokine precursors, cell receptors, fibrin, vitronectin, matrix proteoglycans, cationic antimicrobial peptides, and immunoglobulins, thereby contributing to endothelial and epidermal damage, tissue destruction, and bacterial dissemination. [53][54][55] SpeB enzymatic activity also releases fragments of fibrinogen-complexed M1 protein [fibrinogen-M1], thereby contributing to vascular leakage and host tissue damage. 52 However, at the same time, we detected virtually no grab transcripts, which encode a host protease inhibitor ␣ 2 -macroglobulin-binding bacterial surface protein designated GRAB.…”

Section: Abundant Gas Transcripts In Soft Tissue Infectionmentioning

confidence: 99%

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Graham

Virtaneva

Porcella

et al. 2006

The American Journal of Pathology

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Molecular mechanisms mediating group A Streptococcus (GAS)-host interactions remain poorly understood but are crucial for diagnostic, therapeutic, and vaccine development. An optimized high-density microarray was used to analyze the transcriptome of GAS during experimental mouse soft tissue infection. The transcriptome of a wild-type serotype M1 GAS strain and an isogenic transcriptional regulator knockout mutant (covR) also were compared. Array datasets were verified by quantitative real-time reverse transcriptase-polymerase chain reaction and in situ immunohistochemistry. The results unambiguously demonstrate that coordinated expression of proven and putative GAS virulence factors is directed toward overwhelming innate host defenses leading to severe cellular damage. We also identified adaptive metabolic responses triggered by nutrient signals and hypoxic/acidic conditions in the host, likely facilitating pathogen persistence and proliferation in soft tissues. Key discoveries included that oxidative stress genes, virulence genes, genes related to amino acid and maltodextrin utilization, and several two-component transcriptional regulators were highly expressed in vivo. This study is the first global analysis of the GAS transcriptome during invasive infection. Coupled with parallel analysis of the covR mutant strain, novel insights have been made into the regulation of GAS virulence in vivo, resulting in new avenues for targeted therapeutic and vaccine research.

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“…Some bacterial pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis cause degradation of PAI-1 during invasion [24][25][26]. Bacterial proteases also degrade Vn during invasion [27,28], but there is no information available on degradation of the PAI-1/Vn complex. Recently it was shown that proteins of the omptins family (bacterial surface proteases) including plasminogen activator (Pla) of Yersinia pestis, PgtE of Salmonella typhimurium, and Kop of K. pneumoniae can degrade the PAI-1/Vn complex in vitro [19].…”

Section: The Pai-i/vn Complex and Bacterial Pathogenesismentioning

confidence: 99%

Vitronectin in host pathogen interactions and antimicrobial therapeutic applications

Singh

Riesbeck

2011

Open Life Sciences

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Vitronectin (Vn) is a multifunctional glycoprotein profusely present in serum and bound to epithelial cell surfaces. It plays an important role in cell migration, tissue repair and regulation of membrane attack complex (MAC) formation. In the last decade the role of Vn has been extensively investigated in eukaryotic signalling and cell migration leading to the possibility of developing novel anticancer drugs. In parallel, several studies have suggested that pathogens utilize Vn in invasion of the host. Here we review the properties of Vn and its role in host-pathogen interactions that might be a future target for therapeutic intervention.

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A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin

Cited by 212 publications

References 70 publications

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation

Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection

Vitronectin in host pathogen interactions and antimicrobial therapeutic applications

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