The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module

Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H. P.; Whisstock, James C.; Baker, Edward N.; Kreikemeyer, Bernd

doi:10.1074/jbc.m112.376434

Cited by 19 publications

(32 citation statements)

References 51 publications

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“…Immediately upstream of the sag operon, we identified a 3.3-kb deletion in the epf gene (Fig. 2), which codes for a cell surface adhesion molecule (10). We confirmed this deletion by performing a longrange PCR (Fig.…”

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confidence: 59%

Severe Soft Tissue Infection Caused by a Non-Beta-Hemolytic Streptococcus pyogenes Strain Harboring a Premature Stop Mutation in the sagC Gene

et al. 2013

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gWe recovered a non-beta-hemolytic Streptococcus pyogenes strain from a severe soft tissue infection. In this isolate, we detected a premature stop codon within the sagC gene of the streptolysin S (SLS) biosynthetic operon. Reintroduction of full-length sagC gene on a plasmid vector restored the beta-hemolytic phenotype to our clinical isolate, indicating that the point mutation in sagC accounted for loss of hemolytic activity. To the best of our knowledge, this is the first report to demonstrate that a severe soft tissue infection can be caused by a non-beta-hemolytic S. pyogenes strain lacking a functional SagC. CASE REPORTA 33-year-old man developed pain and swelling after an insect bite to his left forearm. Conservative therapy on an outpatient basis was initiated involving oral roxithromycin and splinting with a cast. The past medical history was uneventful except for a herniated intervertebral disc and arterial hypertension. Except for the prescribed antibiotic, the patient was on no other medication. After 1 week of treatment without any improvement, the patient was referred to the Department of Plastic and Hand Surgery with an abscess on the distal left forearm.On examination, the obese patient (body mass index [BMI], 32 kg/m 2 ) was afebrile. His blood pressure was 140/80 mm Hg, and his pulse was 80 beats per minute. According to the patient, there had previously been pronounced lymphangitis involving the forearm that had improved by the time of presentation to our department. Around the distal forearm, there was an abscess with central soft tissue necrosis (Fig. 1A). The surrounding soft tissue was erythematous, swollen, and tender (Fig. 1A). The sensation of light touch was intact, and the patient was able to move his fingers. There was no crepitation. Lab tests revealed a leukocytosis (11.17/ nl; normal range, 4 to 10/nl) and an elevated C-reactive protein level (52.4 mg/liter; normal range, Ͻ5 mg/liter).Emergency surgery with abscess incision and drainage was performed. Necrotic tissue was removed. Upon further surgical exploration, the peritendineous area surrounding the flexor carpi radialis and the palmaris longus tendons showed extensive pannus formation extending to and involving the loose tissue surrounding the radial artery, suggesting a longer duration of the infectious process prior to surgery. Tenolysis and microsurgical arteriolysis of the radial artery were performed meticulously, and surgical débridement of the abscess was achieved. Tissue specimens were sent for Gram staining and bacterial culture, followed by placement of drains for irrigation and suction of the wound bed.An antibiotic regimen with amoxicillin-clavulanic acid was initiated empirically and continued for 2 weeks. The patient fully recovered and was discharged. Since surgical débridement left only a small defect, no plastic surgery was necessary and the wound healed uneventfully.Direct examination of the surgical tissue specimen revealed abundant neutrophils and Gram-positive cocci ordered in chains. Cultures of surgical...

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confidence: 59%

Severe Soft Tissue Infection Caused by a Non-Beta-Hemolytic Streptococcus pyogenes Strain Harboring a Premature Stop Mutation in the sagC Gene

et al. 2013

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“…However, speC and sdp1 were carried by different prophages in the different groups (Supplementary Figure 2). In comparison with “close outlier” strains, the epidemic clone had 1 SNP in the surface protein–encoding epf gene predicted to result in a D929E amino acid substitution in the predicted translated sequence of this protein factor involved in keratinocyte adhesion and internalization [33]. Additionally, “close outliers” and epidemic strains differed by the presence of nonsynonymous SNPs in the 2 component regulator–encoding gene vicR , in sagD , a gene involved in streptolysin production, and in the global regulator–encoding gene ropB.…”

Section: Resultsmentioning

confidence: 99%

Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease

Teatero

McGeer

Tyrrell

et al. 2018

Open Forum Infectious Diseases

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BackgroundThe number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively.MethodsWe analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide.ResultsGenome analysis showed that highly clonal emm74 strains, genetically different from emm74 organisms previously circulating in Canada, were responsible for a country-wide epidemic of >160 invasive disease cases. The emerging clone belonged to multilocus sequence typing ST120. The analysis also revealed dissemination patterns of emm74 subclonal lineages across Canadian provinces. Clinical data analysis indicated that the emm74 epidemic disproportionally affected middle-aged or older male individuals. Homelessness, alcohol abuse, and intravenous drug usage were significantly associated with invasive emm74 infections.ConclusionsIn a period of 20 months, an emm74 GAS clone emerged and rapidly spread across several Canadian provinces located more than 4500 km apart, causing invasive infections primarily among disadvantaged persons.

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“…No. B5XKN1), originally identified in serotype M49 and confirmed in strain 591, has been shown to bind immobilized Pg [28]. The presence of Epf has been shown to increase the ability of strain 591 cells to adhere to and internalize into human keratinocytes and binds Pg with a determined K d value of 0.28 μM, which is physiologically relevant, as Pg circulates at a concentration of 2 μM [29].…”

Section: Resultsmentioning

confidence: 99%

In Vivo Tracking of Streptococcal Infections of Subcutaneous Origin in a Murine Model

et al. 2015

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Purpose Generation of plasmin in vivo by Streptococcus pyogenes is thought to localize the active protease complexes to the pathogen surface to aid in tissue dissemination. Here, we chose to follow cutaneous streptococcal infections by the use of non-invasive bioluminescence imaging to determine if this pathogen can be followed by this approach and the extent of bacterial spread in the absence of canonical plasminogen activation by streptokinase. Procedures Mice were injected subcutaneously with either bioluminescent strains of streptococci, namely Xen20 and Xen10 or S. pyogenes ALAB49. Bioluminescence imaging was performed daily and results were correlated with microbiological and histological analyses. Results Comparative analysis of chronologic non-invasive datasets indicated that Xen20 did not disseminate from the initial infection site. Contrary to this, microbiological and histological analyses of Xen20 mice for total bacterial burden indicated sepsis and widespread pathogen involvement. Conclusions The use of bioluminescence in microbe-based studies requires genomic and pathologic characterization to correlate imaging results with underlying pathology.

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The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module

Cited by 19 publications

References 51 publications

Severe Soft Tissue Infection Caused by a Non-Beta-Hemolytic Streptococcus pyogenes Strain Harboring a Premature Stop Mutation in the sagC Gene

Severe Soft Tissue Infection Caused by a Non-Beta-Hemolytic Streptococcus pyogenes Strain Harboring a Premature Stop Mutation in the sagC Gene

Canada-Wide Epidemic of emm74 Group A Streptococcus Invasive Disease

In Vivo Tracking of Streptococcal Infections of Subcutaneous Origin in a Murine Model

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