Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.2.3.23 (GAS)
957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the absence of conclusive proof, the incidence of necrotizing fasciitis and myositis due to GAS may be increasing, possibly related to shifts in the proportion of GAS isolates of M-Types 1 and 3. These M-types (or the production of exotoxins and proteases associated with them) may lead to severe GAS infections in individuals who lack immunity. Recent television and newspaper reports underscore the potential virulence of GAS even in young and previously well individuals although they do this at the expense of raising fear in the general population. It is unfortunate that these reports often fail to emphasize the rarity with which GAS causes myositis and fasciitis. The overall incidence of these dreadful diseases is very low. In fact, by extrapolating the CDC estimates, we suspect that only 14-40 cases of GAS-induced myositis or fasciitis occur annually in North Carolina. Each of these infections is a true calamity for the affected patients and their physicians, but together they represent only a tiny fraction of all GAS infections that occur in North Carolinians each year. It is relatively easy to separate uncomplicated streptococcal cellulitis from GAS-induced fasciitis and/or myositis by bedside exam and old-fashioned clinical judgment. Prompt and aggressive surgical debridement and antibiotic therapy are needed for all patients with myositis and/or fasciitis due to GAS; others can be treated with simple beta-lactam antibiotics and careful observation.
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PMID:Necrotizing fasciitis and myositis caused by group A streptococci. Epidemiology, diagnosis, and treatment of "flesh-eating bacteria". 780 56

A recent study with isogenic strains constructed by recombinant DNA strategies unambiguously documented that a highly conserved extracellular cysteine protease expressed by Streptococcus pyogenes (group A Streptococcus [GAS]) is a critical virulence factor in a mouse model of invasive disease (S. Lukomski, S. Sreevatsan, C. Amberg, W. Reichardt, M. Woischnik, A. Podbielski, and J. M. Musser, J. Clin. Invest. 99:2574-2580, 1997). To facilitate further investigations of the streptococcal cysteine protease, recombinant proteins composed of a 40-kDa zymogen containing a C192S amino acid substitution that ablates enzymatic activity, a 28-kDa mature protein with the C192S replacement, and a 12-kDa propeptide were purified from Escherichia coli containing His tag expression vectors. The recombinant C192S zymogen retained apparently normal structural integrity, as assessed by the ability of purified wild-type streptococcal cysteine protease to process the 40-kDa molecule to the 28-kDa mature form. All three recombinant purified proteins retained immunologic reactivity with polyclonal and monoclonal antibodies. Humans with a diverse range of invasive disease episodes (erysipelas, cellulitis, pneumonia, bacteremia, septic arthritis, streptococcal toxic shock syndrome, and necrotizing fasciitis) caused by six distinct M types of GAS seroconverted to the streptococcal cysteine protease. These results demonstrate that this GAS protein is expressed in vivo during the course of human infections and thereby provide additional evidence that the cysteine protease participates in host-pathogen interactions in some patients.
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PMID:Expression and characterization of group A Streptococcus extracellular cysteine protease recombinant mutant proteins and documentation of seroconversion during human invasive disease episodes. 945 39

Streptococcus pyogenes (group A streptococcus--GAS) is a common cause of necrotizing fasciitis (NF)--a severe infection of the subcutaneous soft tissue. The purpose of this study was to determine if the topical therapy ultraviolet light C (UVC) is effective in killing GAS in vitro and to evaluate the most effective treatment parameters for use with UVC therapy. Five replications of GAS at 10(8) organisms/mL were plated. The cultures were treated with a UVC light 1 inch from the surface. Irradiation times were as follows: 0, 2, 3, 4, 5, 15, 30, 45, 60, 90, 120, and 180 seconds. Bacterial cultures were incubated and colony counts performed. A second set of GAS cultures were exposed to UVC for 30, 90, and 120 seconds either once daily (qd) or twice daily (bid). Kill rates were 99.9% for GAS at 4 seconds to 180 seconds. Kill rates of 99.9% were also obtained at 30 seconds and 90 seconds when UVC treatment was given either qd or bid. This data indicates that UVC is bactericidal for GAS at times as short as 4 seconds. In addition, UVC treatment was not effective when administered through thin film dressings.
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PMID:The effects of UVC irradiation on group A streptococcus in vitro. 1068 52

The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period. Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.
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PMID:Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis. 1120 10

After years of steadily declining morbidity and mortality due to group A streptococcal infections, a resurgence of severe, invasive disease has been ongoing since 1980, leading to the recognition of streptococcal shock syndrome (STSS), necrotizing fasciitis, the most severe form of invasive infection. The patients suffer from rapid local deep soft tissue destruction, severe septic shock and multi organ failure. The increased incidence of these infections has been accompanied by remarkable vigor in virulence and severity of the disease. The reason for this impressive change in the epidemiology and clinical manifestation of group A streptococcal infections remains unknown. The possible etiological factor is changing in virulence factor or the lack of protective immunity of the population (immunocompromise) against the invasive strains. We describe a severe necrotizing fasciitis of a 41-year-old previously immunocompromised woman. The patient developed severe septic shock, multi organ failure and perineal and lower abdominal skin, fat and fascia necrosis due to mixed GAS (aerob, anaerob) infection of the perineum and the Bartholini glands. After an aggressive surgical debridement, antibiotic and supportive therapy the generalised and local infection was treated.
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PMID:[Flesh-eating bacteria infection of an immunocompromised patient]. 1172 40

A 30-year-old woman at 25 weeks gestation presented to the labour ward complaining of abdominal pain and a painful bruise in her right groin. Over the course of several hours, she developed rapidly spreading necrotising fasciitis of the right thigh. She required emergency radical debridement of the thigh and caesarean delivery of a dead fetus. She was admitted to the intensive care unit (ICU) with septic shock, where she received ventilatory and inotropic support. Streptococcus pyogenes was isolated from the infected tissue and a diagnosis of group A streptococcal toxic shock-like syndrome (GAS TS-LS) was confirmed. Following acute and rapid haemodynamic deterioration, plasmapheresis was given for 6 days, after which the patient's general condition improved and vasoconstrictor requirement was significantly reduced. Subsequently, immunoglobulin was given intravenously for thrombocytopenia, following which the platelet count steadily improved. Despite the development of acute renal failure, acute respiratory distress syndrome and a left hemiplegia, the patient made a remarkable recovery. She was later transferred to a plastic surgical unit for split skin-grafting. The importance of early diagnosis and aggressive treatment of GAS TS-LS is emphasized and the place of plasmapheresis and intravenous immunoglobulin therapy in this condition is discussed.
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PMID:Necrotising fasciitis and group A streptococcus toxic shock-like syndrome in pregnancy: treatment with plasmapheresis and immunoglobulin. 1532 Nov 56

Streptococcus pyogenes (the group A streptococcus [GAS]) is a medically significant pathogen of humans, causing a range of diseases from pharyngitis to necrotizing fasciitis. Several important GAS virulence genes are under the control of a pleiotropic regulator called Mga, or the multiple gene regulator of GAS, including the gene encoding the streptococcal collagen-like protein, or sclA. Analysis of the genome sequence upstream of sclA revealed two potential Mga-binding sites with homology to the published Mga-binding element, which were called PsclA-I (distal) and PsclA-II (proximal) based on their location relative to a predicted start of transcription. Primer extension was used to confirm that the Mga-dependent transcriptional start site for sclA was located adjacent to the proximal PsclA-II binding site. By using overlapping PsclA promoter probes and purified Mga-His fusion protein, it was shown by electrophoretic mobility shift assays that, unlike other Mga-regulated promoters, Mga binds only to a distal DNA-binding site (PsclA-I). Binding of Mga to PsclA-I could be competed with cold probes corresponding to known Mga-regulated promoters (Pemm, PscpA, and Pmga) but not with a nonspecific probe or the proximal PsclA-II fragment. With the use of a plasmid-based green fluorescent protein transcriptional reporter system, the full-length PsclA was not sufficient to reproduce normal Mga-regulated activation. However, studies using a single-copy gusA transcriptional reporter system integrated at the native sclA chromosomal locus clearly demonstrated that the distal PsclA-I binding site is required for Mga regulation. Therefore, PsclA represents a new class of Mga-regulated promoters that requires a single distal binding site for activation.
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PMID:Transcriptional activation of sclA by Mga requires a distal binding site in Streptococcus pyogenes. 1554 55

Group A Streptococcus is characterized by the ability to cause a diverse number of human infections including pharyngitis, necrotizing fasciitis, toxic shock syndrome, and acute rheumatic fever, yet the regulation of streptococcal genes involved in disease processes and survival in the host is not completely understood. Genome scale analysis has revealed a complex regulatory network including 13 two-component regulatory systems and more than 100 additional putative regulators, the majority of which remain uncharacterized. Among these is the streptococcal regulator of virulence, Srv, the first Group A Streptococcus member of the Crp/Fnr family of transcriptional regulators. Previous work demonstrated that the loss of srv resulted in a significant decrease in Group A Streptococcus virulence. To begin to define the gene products influenced by Srv, we combined microarray and two-dimensional gel electrophoresis analysis. Loss of srv results in a chromosome wide reduction of gene transcription and changes in the production of the extracellular virulence factors Sic (streptococcal inhibitor of complement) and SpeB (cysteine proteinase). Sic levels are reduced in the srv mutant, whereas the extracellular concentration and activity of SpeB is increased. These data link Srv to the increasingly complex GAS regulatory network.
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PMID:Inactivation of the group A Streptococcus regulator srv results in chromosome wide reduction of transcript levels, and changes in extracellular levels of Sic and SpeB. 1699 24

Streptococcus pyogenes (group A streptococcus [GAS]) is a versatile human pathogen, and emm1/sequence type 28 (ST28) is the most frequently isolated type from GAS infections. The emm1/ST28 strain is associated with necrotizing fasciitis and streptococcal toxic shock syndrome. Growth-phase regulation is one of the important regulatory mechanisms in GAS, which controls gene expression at restricted phases of growth. CovRS, a two-component regulatory system, is considered the regulator of streptococcal pyrogenic exotoxin B (SpeB) and is thought to be activated in the exponential phase of growth. In the present study, Northern hybridization analysis showed that 52% of the analyzed GAS strains expressed covR at the exponential phase, but 48% of the strains expressed covR at the early stationary phase of growth. Strains transcribing covR at the early stationary phase showed better growth and earlier SpeB expression than the other group of strains. Multilocus sequence typing and pulsed-field gel electrophoresis analysis showed only emm1/ST28 strains (which comprise a clonal cluster) were expressing covR at the early stationary phase of growth, indicating that emm1/ST28 strains have special characteristics which may be related to their worldwide distribution.
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PMID:emm1/sequence type 28 strains of group A streptococci that express covR at early stationary phase are associated with increased growth and earlier SpeB secretion. 1971 Feb 71

Group A Streptococcus is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Cell wall anchored pili were recently described in several species of pathogenic streptococci, and in the case of GAS, these surface appendages were demonstrated to facilitate epithelial cell adherence. Here we use targeted mutagenesis to evaluate the contribution of pilus expression to virulence of the globally disseminated M1T1 GAS clone, the leading agent of both GAS pharyngitis and severe invasive infections. We confirm that pilus expression promotes GAS adherence to pharyngeal cells, keratinocytes, and skin. However, in contrast to findings reported for group B streptococcal and pneumococcal pili, we observe that pilus expression reduces GAS virulence in murine models of necrotizing fasciitis, pneumonia and sepsis, while decreasing GAS survival in human blood. Further analysis indicated the systemic virulence attenuation associated with pilus expression was not related to differences in phagocytic uptake, complement deposition or cathelicidin antimicrobial peptide sensitivity. Rather, GAS pili were found to induce neutrophil IL-8 production, promote neutrophil transcytosis of endothelial cells, and increase neutrophil release of DNA-based extracellular traps, ultimately promoting GAS entrapment and killing within these structures.
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PMID:M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment. 1996 Jan 75


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