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)

We used an ELISA to determine the levels of specific anti-GAS carbohydrate IgG, IgM and IgA in 34 patients with acute rheumatic fever (ARF) with or without carditis, in 15 patients with acute glomerulonephritis (AGN) and in 18 control patients with noncomplicated GAS pharyngitis. Patients with ARF and AGN showed a significantly higher geometric mean titer as well as a higher frequency of elevated Ig of the IgG, IgM and IgA A-CHO class antibodies during the acute stage of this disease, when compared to controls. The IgM and IgA geometric means of the antibody were higher in ARF with carditis patients as compared to the non-carditis or AGN patients; however, the differences were not significant. In addition a lower frequency of antibody decline was observed in ARF with carditis patients who were seen in follow-up after a 1-year period, supporting previous observations of the persistence of this antibody in patients with rheumatic heart disease.
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PMID:Immunoglobulin isotype response to the group-A streptococcal carbohydrate in humans. 305 40

Besides group A (GAS), Lancefield group C beta-haemolytic streptococci (GCS) have been implicated as a causative agent in outbreaks of purulent pharyngitis. In this study we have investigated a class CI M protein of a Streptococcus dysgalactiae1:256, revealed that 26% of these sera showed serological cross-reactivity between a 68-kDa cartilage protein and the N-terminal part of MC. Only 8% of the sera of healthy patients showed this property. In additional, MC also cross-reacted with antibodies recognising epidermal keratins. The cross-reacting 68-kDa protein from cartilage was different from human serum albumin, but was recognised with anti-vimentin immune serum. The MC was cloned and the gene sequenced. By using PCR, recombinant gene fragments encoding characteristic peptide fragments of MC were expressed in Escherichia coli. The peptides were used to map the binding sites for plasma proteins and to locate the cross-reacting epitopes on the MC molecule. In consequence, sequence alignments revealed that MC shared homologous regions with vimentin and different keratins. Our data, obtained with MC, suggest that not only infections with GAS but also infections with GCS and possibly GGS (the latter species can also produce class CI M-like proteins) may be responsible for the formation of streptococcal-associated sequel diseases.
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PMID:M protein of a Streptococcus dysgalactiae human wound isolate shows multiple binding to different plasma proteins and shares epitopes with keratin and human cartilage. 1051 39

In addition to beta-haemolytic streptococci belonging to Lancefield group A (Streptococcus pyogenes, GAS), human isolates of group C (GCS) and group G (GGS) streptococci (S. dysgalactiae subsp. equisimilis) have been implicated as causative agents in outbreaks of purulent pharyngitis, of wound infections and recently also of streptococcal toxic shock-like syndrome. Very little is known about the organisation of the genomic region in which the emm gene of GCS and GGS is located. We have investigated the genome sequences flanking the emm gene in GCS by sequencing neighbouring fragments obtained by inverse PCR. Our sequence data for GCS strains 25287 and H46A revealed two types of arrangement in the emm region, which differ significantly from the known types of mga regulon in GAS. We named this segment of the genome mgrC (for multigene regulon-like segment in group C streptococci). In strains belonging to the first mgrC type (prototype strain 25287) the emm gene is flanked up-stream by mgc, a gene that is 61% identical to the mga gene of GAS. A phylogenetic analysis of the deduced protein sequences showed that Mgc is related to Mga proteins of various types of GAS but forms a distinct cluster. Downstream of emm, the mgrC sequence region is bordered by rel. This gene encodes a protein that functions in the synthesis and degradation of guanosine 3',5' bipyrophosphate (ppGpp) during the stringent regulatory response to amino acid deprivation. In the second mgrC type (prototype strain H46A), the genes mgc and emm are arranged as in type 1. But an additional ORF (orf) is inserted in opposite orientation between emm and rel. This orf shows sequence homology to cpdB, which is present in various microorganisms and encodes 2',3' cyclo-nucleotide 2'-phosphodiesterase. PCR analysis showed that these two mgrC arrangements also exist in GGS. Our sequence and PCR data further showed that both types of mgrC region in GCS and GGS are linked via rel to the streptokinase region characterised recently in strain H46A. A gene encoding C5a peptidase, which is present at the 3' end of the mga regulon in GAS, was not found in the mgrC region identified in the GCS and GGS strains investigated here.
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PMID:Genetic organisation of the M protein region in human isolates of group C and G streptococci: two types of multigene regulator-like (mgrC) regions. 1066 58

A number of options exist for reducing the frequency of antibiotic dosing and shortening the course of treatment of GAS pharyngitis. All oral agents are more costly than oral penicillin and have a broader spectrum of antimicrobial activity. These issues must be weighed against the convenience of these treatment regimens. At this time penicillin remains the drug of choice for acute streptococcal pharyngitis. Oral penicillin V can be given twice daily for 10 days. Intramuscular benzathine penicillin is inexpensive and obviates any concerns about compliance. For penicillin-allergic patients, twice daily erythromycin for 10 days is preferred but azithromycin once a day for 5 days is a reasonable (but expensive) alternative.
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PMID:Convenient schedules and short course treatment of acute streptococcal pharyngitis. 1087 76

In the latter half of the 20th century, the clinical importance of variation in the virulence of strains of GAS has been clearly demonstrated. Although still obscure, the pathogenesis of ARF requires immunologically significant infection of the throat by virulent GAS strains. These strains contain large hyaluronate capsules and large M-protein molecules. The latter contain epitopes cross-reactive with host tissues, and also contain superantigenic toxic moieties. In areas where ARF has become rare, GAS pharyngitis continues to be common but is caused predominantly by GAS strains of relatively low virulence. These, however, may colonize the throat avidly and stubbornly. Molecularly distinct pyoderma strains may cause acute glomerulonephritis, but they are not rheumatogenic even though they may secondarily infect the throat. In developing countries with a very high incidence of rheumatic heart disease, identification of the prevalent rheumatogenic GAS strains and development of a multivalent vaccine against them is currently an interesting strategy. Pending vaccine development, intense primary and secondary penicillin prophylaxis should continue to be sharply focused on populations with the highest prevalence of RHD as such measures may often succeed in driving away the most virulent rheumatogenic clones of GAS from their midst.
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PMID:Can we eradicate rheumatic fever in the 21st century? 1142 92

The important human pathogen Streptococcus pyogenes (the group A streptococcus or GAS) causes diseases ranging from mild, self-limiting pharyngitis to severe invasive infections. Regulation of the expression of GAS genes in response to specific environmental differences within the host is probably key in determining the course of the infectious process, however, little is known of global regulators of gene expression in GAS. Although secondary RNA polymerase sigma factors act as global regulators of gene expression in many other bacteria, none has yet been isolated from the GAS. The newly available GAS genome sequence indicates that the only candidate secondary sigma factor is encoded by two identical open reading frames (ORFS). These ORFS encode a protein that is 40% identical to the transcription factor ComX, believed to act as an RNA polymerase sigma factor in Streptococcus pneumoniae. To test whether the GAS ComX homologue functions as a sigma factor, we cloned and purified it from Escherichia coli. We found that in vitro, this GAS protein, which we call sigmaX, directed core RNA polymerase from Bacillus subtilis to transcribe from two GAS promoters that contain the cin-box region, required for transcription by S. pneumoniae ComX in vivo. On the other hand, GAS sigmaX did not promote transcription of a GAS promoter (hasA) expected to be dependent on sigmaA, the housekeeping or primary RNA polymerase sigma factor. Addition of monoclonal antibody that inhibited sigmaA-directed transcription had no effect on sigmaX-directed transcription, showing that the latter was not the result of contaminating sigmaA. Transcription of both cin-box-containing promoters initiated downstream of the cin-box and two different single basepair substitutions in the cin-box of the cinA promoter each caused a severe reduction of sigmaX-directed transcription in vitro. Thus, the cin-box is required for sigmaX-directed transcription.
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PMID:A secondary RNA polymerase sigma factor from Streptococcus pyogenes. 1170 70

Streptococcus pyogenes (GAS) causes about 90% of streptococcal human infections while group C (GCS) and G (GGS) streptococci can be pathogenic for different mammalians. Especially the human pathogenic GCS and GGS, Streptococcus dysgalactiae, subsp. equisimilis, account for 5-8% of the human streptococcal diseases like wound infections, otitis media, purulent pharyngitis and also streptococcal toxic shock syndrome. A defined superantigen so far was not identified in GCS and GGS strains. In the present investigation we screened DNA of GCS and GGS human isolates for the presence of genes for streptococcal pyrogenic exotoxins (spe) by hybridisation with probes that stand for the GAS genes speA, speC, speZ (smeZ), speH, speG, speI, speJ and ssa. In many GCS and GGS strains we found positive reactions with the probes speG, speJ and ssa, but not with the probes for the remaining genes under investigation. PCR amplification with subsequent sequence analysis of the PCR fragments revealed only the presence of the gene speG in GCS and GGS strains, while no DNA fragments specific for speJ and ssa could be amplified. Additionally, the upstream and downstream regions flanking speG in GGS strain 39072 were sequenced. Remarkable differences were found in the neighbourhood of speG between GAS and GGS sequences. Downstream of speG we identified in strain GGS 39072 two new open reading frames encoding proteins with no similarity to protein sequences accessible in the databases so far. In the compared GAS strains SF370 and MGAS8232, this segment, apart from some small fragments, had been deleted. Our analysis suggests that a gene transfer from GGS to GAS has preceded following deletion of the two genes orf1 and orf2 in GAS.
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PMID:Superantigen-like gene(s) in human pathogenic Streptococcus dysgalactiae, subsp equisimilis: genomic localisation of the gene encoding streptococcal pyrogenic exotoxin G (speG(dys)). 1238 68

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

Streptococcus pyogenes (group A streptococci; GAS) recovered from paediatric pharyngitis (101 isolates) and asymptomatic children (79 isolates) in the same geographical area and period, as well as isolates collected during an enhanced national surveillance programme for GAS invasive diseases (79 isolates), were screened for the incidence of the streptococcal pyrogenic exotoxin (spe) genes speA and speC, as well as the macrolide-resistance genes erm(B), erm(A) subclass erm(TR) and mef(A), and typed by emm sequencing. The speA gene was detected with comparable incidence among throat isolates (13.9 % of asymptomatic children and 16.8 % of pharyngitis isolates) and in 25 % of invasive cases; in contrast, speC incidence was, surprisingly, higher in paediatric populations (55.4 % in pharyngitis isolates and 65.8 % in asymptomatic children) than in invasive isolates (30 %; P < 0.0001). Macrolide resistance was detected in 26.6, 38.0 and 37.6 % of strains belonging to invasive, asymptomatic and pharyngitis populations, respectively. The different incidences of exotoxin and antibiotic-resistance genes among populations did not appear to have an intrinsic clinical significance, but may reflect the propensity of these traits to be associated with certain emm types independent of the source from which the strains were isolated. Further investigations with larger emm-type populations are warranted to confirm this.
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PMID:Association of group A streptococcal emm types with virulence traits and macrolide-resistance genes is independent of the source of isolation. 1615 43

In this study, we analyzed the antimicrobial resistance properties and T antigenic types of 511 isolates collected in Lisbon district, Portugal, from throat swabs of healthy subjects (n=341), during 2000-2002 and from diverse infection sites (n=170) of outpatients and inpatients, during 1999-2002. Erythromycin resistance was higher in tonsillitis/pharyngitis (27.4%) and skin infection isolates (21.1%), than in carriage and invasive isolates (<or=10%). Differences in erythromycin resistance among children and adults were noticed only for carriage isolates (9.3% in children and 21.1% in adults). Most erythromycin-resistant isolates from carriage (82.4%) and tonsillitis/pharyngitis (71.9%) showed the M phenotype. All M phenotype isolates (n=53) carried mef(A), whereas all MLS(B) phenotype isolates (n=19) carried erm(B) and not erm(A). Resistance to tetracycline [mediated by tet(M) in most isolates] was <or=6% in tonsillitis/pharyngitis and carriage isolates, 36.8% in skin infection isolates, and 44.1% in invasive isolates. The M phenotype increased since 2000, linked to a decrease of tetracycline resistance, and was predominantly associated with T1 in 2000-2001 and T12 in 2002 among carriage isolates, and with T8/25/Imp19 through 2000-2002 among tonsillitis/pharyngitis isolates. The majority (53%) of the tetracycline-resistant invasive isolates were nontypable. All isolates were susceptible to penicillin and chloramphenicol. This study showed that tetracycline and macrolide resistance frequency and phenotypes differ among GAS from various origins and changed over time. Moreover, T typing suggested that most drug-resistant isolates causing oropharyngeal carriage are distinct from the majority of isolates causing noninvasive and invasive infection.
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PMID:Group A Streptococci from carriage and disease in Portugal: evolution of antimicrobial resistance and T antigenic types during 2000-2002. 1635 96


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