scholarly journals Changes in emm types and superantigen gene content of Streptococcus pyogenes causing invasive infections in Portugal

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
A. Friães ◽  
◽  
J. Melo-Cristino ◽  
M. Ramirez
Keyword(s):  
Streptococcus Pyogenes ◽  
Susceptibility Testing ◽  
Gene Profiling ◽  
Short Term ◽  
Genomic Variants ◽  
Increasing Trend ◽  
Invasive Infections ◽  
Group A ◽  
Profile Changes ◽  
Clonal Composition

AbstractFluctuations in the clonal composition of Group A Streptococcus (GAS) have been associated with the emergence of successful lineages and with upsurges of invasive infections (iGAS). This study aimed at identifying changes in the clones causing iGAS in Portugal. Antimicrobial susceptibility testing, emm typing and superantigen (SAg) gene profiling were performed for 381 iGAS isolates from 2010–2015. Macrolide resistance decreased to 4%, accompanied by the disappearance of the M phenotype and an increase of the iMLSB phenotype. The dominant emm types were: emm1 (28%), emm89 (11%), emm3 (9%), emm12 (8%), and emm6 (7%). There were no significant changes in the prevalence of individual emm types, emm clusters, or SAg profiles when comparing to 2006–2009, although an overall increasing trend was recorded during 2000–2015 for emm1, emm75, and emm87. Short-term increases in the prevalence of emm3, emm6, and emm75 may have been driven by concomitant SAg profile changes observed within these emm types, or reflect the emergence of novel genomic variants of the same emm types carrying different SAgs.

scholarly journals Distribution of emm type and antibiotic susceptibility of group A streptococci causing invasive and noninvasive disease

2008 ◽  
Vol 57 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Takeaki Wajima ◽  
Somay Y. Murayama ◽  
Katsuhiko Sunaoshi ◽  
Eiichi Nakayama ◽  
Keisuke Sunakawa ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Macrolide Antibiotic ◽  
Group A Streptococcus ◽  
Acute Otitis Media ◽  
Toxic Shock ◽  
Medical Institutions ◽  
Invasive Infections ◽  
Group A ◽  
Resistant Strains ◽  
Emm Type

To determine the prevalence of macrolide antibiotic and levofloxacin resistance in infections with Streptococcus pyogenes (group A streptococcus or GAS), strains were collected from 45 medical institutions in various parts of Japan between October 2003 and September 2006. Four hundred and eighty-two strains from patients with GAS infections were characterized genetically. Strains were classified into four groups according to the type of infection: invasive infections (n=74) including sepsis, cellulitis and toxic-shock-like syndrome; acute otitis media (AOM; n=23); abscess (n=53); and pharyngotonsillitis (n=332). Among all strains, 32 emm types were identified; emm1 was significantly more common in invasive infections (39.2 %) and AOM (43.5 %) than in abscesses (3.8 %) or pharyngotonsillitis (10.2 %). emm12 and emm4 each accounted for 23.5 % of pharyngotonsillitis cases. Susceptibility of GAS strains to eight β-lactam agents was excellent, with MICs of 0.0005–0.063 μg ml−1. Macrolide-resistant strains accounted for 16.2 % of all strains, while the percentages of strains possessing the resistance genes erm(A), erm(B) and mef(A) were 2.5 %, 6.2 % and 7.5 %, respectively. Although no strains with high resistance to levofloxacin were found, strains with an MIC of 2–4 μg ml−1 (17.4 %) had amino acid substitutions at either Ser-79 or Asp-83 in ParC. These levofloxacin-intermediately resistant strains included 16 emm types, but macrolide-resistant strains were more likely than others to represent certain emm types.

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

scholarly journals Prevalence and Characterization of Invasive Isolates of Streptococcus pyogenes with Reduced Susceptibility to Fluoroquinolones

2005 ◽  
Vol 49 (5) ◽  
pp. 2130-2132 ◽  
Author(s):  
Jeff Powis ◽  
Allison McGeer ◽  
Carla Duncan ◽  
Ryan Goren ◽  
Joyce C. S. de Azavedo ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Susceptibility Testing ◽  
Group A Streptococcus ◽  
Invasive Group ◽  
Group A

ABSTRACT Fluoroquinolone susceptibility testing was performed on invasive group A streptococcus isolates from 1992-1993 and 2003 from Ontario, Canada. None were nonsusceptible to levofloxacin. Two of 153 (1.3%) from 1992-1993 and 7 of 160 (4.4%) from 2003 had a levofloxacin MIC of 2 μg/ml; all nine had parC mutations, and eight were serotype M6.

scholarly journals Cellular Growth Arrest and Efflux Pumps Are Associated With Antibiotic Persisters in Streptococcus pyogenes Induced in Biofilm-Like Environments

2021 ◽  
Vol 12 ◽  
Author(s):  
Caroline Lopes Martini ◽  
Amada Zambrana Coronado ◽  
Maria Celeste Nunes Melo ◽  
Clarice Neffa Gobbi ◽  
Úrsula Santos Lopez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Streptococcus Pyogenes ◽  
Protein Biosynthesis ◽  
Efflux Pumps ◽  
Resistance Mechanisms ◽  
Cellular Growth ◽  
Abiotic Surfaces ◽  
Invasive Infections ◽  
Group A

Streptococcus pyogenes (group A Streptococcus-GAS) is an important pathogen for humans. GAS has been associated with severe and invasive diseases. Despite the fact that these bacteria remain universally susceptible to penicillin, therapeutic failures have been reported in some GAS infections. Many hypotheses have been proposed to explain these antibiotic-unresponsive infections; however, none of them have fully elucidated this phenomenon. In this study, we show that GAS strains have the ability to form antimicrobial persisters when inoculated on abiotic surfaces to form a film of bacterial agglomerates (biofilm-like environment). Our data suggest that efflux pumps were possibly involved in this phenomenon. In fact, gene expression assays by real-time qRT-PCR showed upregulation of some genes associated with efflux pumps in persisters arising in the presence of penicillin. Phenotypic reversion assay and whole-genome sequencing indicated that this event was due to non-inherited resistance mechanisms. The persister cells showed downregulation of genes associated with protein biosynthesis and cell growth, as demonstrated by gene expression assays. Moreover, the proteomic analysis revealed that susceptible cells express higher levels of ribosome proteins. It is remarkable that previous studies have reported the recovery of S. pyogenes viable cells from tissue biopsies of patients presented with GAS invasive infections and submitted to therapy with antibiotics. The persistence phenomenon described herein brings new insights into the origin of therapeutic failures in S. pyogenes infections. Multifactorial mechanisms involving protein synthesis inhibition, cell growth impairment and efflux pumps seem to play roles in the formation of antimicrobial persisters in S. pyogenes.

scholarly journals Impact of M49, Mrp, Enn, and C5a Peptidase Proteins on Colonization of the Mouse Oral Mucosa by Streptococcus pyogenes

1998 ◽  
Vol 66 (11) ◽  
pp. 5399-5405 ◽  
Author(s):  
Yinduo Ji ◽  
Norbert Schnitzler ◽  
Eric DeMaster ◽  
Patrick Cleary
Keyword(s):  
Oral Mucosa ◽  
Streptococcus Pyogenes ◽  
Polymorphonuclear Leukocytes ◽  
Group A Streptococcus ◽  
M Protein ◽  
Insertion Mutation ◽  
Short Term ◽  
Group A ◽  
Isogenic Strains

ABSTRACT Resistance to phagocytosis is a hallmark of virulentStreptococcus pyogenes (group A streptococcus). Surface-bound C5a peptidase reduces recruitment of phagocytes to the site of infection, and hyaluronic acid capsules and/or the M protein limit the uptake of streptococci. In this study the relative impact of M and M-like proteins and the C5a peptidase on the virulence of a serotype M49 strain was assessed. The capacities of isogenic strains with an insertion mutation in emm49; with a deletion mutation in scpA49 (C5a peptidase gene); and with a deletion that removes all three M-like genes, mrp49,emm49, and enn49, to colonize mice and resist phagocytosis were compared. Experiments confirmed results obtained in an earlier study, which showed that the M49 protein was not required for in vitro resistance to phagocytosis, and also showed that the M protein was not required for colonization of mice. Failure to produce all three M-like proteins, M49, Mrp, and Enn49, significantly reduced the ability of these streptococci to resist phagocytosis in vitro but did not significantly alter the persistence of streptococci on the oral mucosa. In vitro experiments indicate that M+ streptococci are phagocytized by polymorphonuclear leukocytes that have been activated with phorbol-12-myristate 13-acetate or recombinant human C5a. This observation may explain the finding that expression of M49 protein is not essential for short-term colonization of the mouse oral mucosa.

scholarly journals Group A β-Haemolytic Streptococcus Infection Presenting with Sore Throat at Paediatric OPD

1970 ◽  
Vol 8 (2) ◽  
pp. 90-92
Author(s):  
R Gurung ◽  
S Budhathoki ◽  
R Amatya ◽  
N Poudyal ◽  
S Shrestha ◽  
...  
Keyword(s):  
Sore Throat ◽  
Streptococcus Pyogenes ◽  
Pediatric Patients ◽  
Susceptibility Testing ◽  
Streptococcal Pharyngitis ◽  
Diffusion Method ◽  
Disc Diffusion Method ◽  
Group A ◽  
Ciprofloxacin Resistance ◽  
Actual Prevalence

Objective: To study the prevalence of streptococcal pharyngitis in pediatric patients presenting with sore throat. Methods: A total of 100 patients aged 5.15 years were enrolled in the study. Verbal consent was obtained to collect specimens. The specimens were collected with the help of sterile cotton tipped swab, cultured in blood agar and chocolate agar as per the guideline. Streptococcus pyogenes was identified on the basis of Gram.s stain and its sensitivity towards 0.04 units of bacitracin disc. Antimicrobial susceptibility testing of the isolates was performed using Kirby Bauer disc diffusion method. Finding: Out of 100 patients which were included, 54 were male and 46 were female. GAS was isolated from 5 patients, of which 3 were male and 2 were female. Of the 5, S. pyogenes strains isolated, 2(66.6%) were found to be resistant to cotrimoxazole. Ciprofloxacin resistance was seen in one isolate. No resistance was detected in gentamycin, cefalexin, penicillin, and erythromycin. Conclusion: The results show that the prevalence of streptococcal pharyngitis is 5% among OPD cases, further study should be conducted in the community to know the actual prevalence of streptococcal pharyngitis. Keywords: Pharyngitis; Prevalence; Streptococcus pyogenes DOI: 10.3126/hren.v8i2.4418 Health Renaissance, May-Aug 2010; Vol 8 (No.2):90-92

scholarly journals Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012

2014 ◽  
Vol 19 (17) ◽  
Author(s):  
L B Olafsdottir ◽  
H Erlendsdóttir ◽  
J Melo-Cristino ◽  
D M Weinberger ◽  
M Ramirez ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Clinical Characteristics ◽  
Population Based ◽  
Host Susceptibility ◽  
Population Based Study ◽  
Virulent Strains ◽  
Invasive Infections ◽  
Group A ◽  
Severe Infections

Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34–4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.

scholarly journals Molecular characterization of Streptococcus pyogenes group A isolates from a tertiary hospital in Lebanon

2014 ◽  
Vol 63 (9) ◽  
pp. 1197-1204 ◽  
Author(s):  
Nathalie M. Karaky ◽  
George F. Araj ◽  
Sima T. Tokajian
Keyword(s):  
Streptococcus Pyogenes ◽  
Susceptibility Testing ◽  
Clinical Manifestations ◽  
Tertiary Hospital ◽  
Human Pathogens ◽  
Genetic Characteristics ◽  
Epidemiological Analysis ◽  
Group A ◽  
Resistant Strains

Streptococcus pyogenes [Group A Streptococcus (GAS)] is one of the most important human pathogens, responsible for numerous diseases with diverse clinical manifestations. As the epidemiology of GAS infections evolves, a rapid and reliable characterization of the isolates remains essential for epidemiological analysis and infection control. This study investigated the epidemiological patterns and genetic characteristics of 150 GAS isolates from a tertiary hospital in Lebanon by emm typing, superantigens (SAgs) detection, PFGE and antibiotic profiling. The results revealed 41 distinct emm types, the most prevalent of which were emm89 (16 %), emm12 (10 %), emm2 (9 %) and emm1 (8 %). Testing for the presence of superantigens showed that speB (87 %), ssa (36 %) and speG (30 %) were predominant. PFGE detected 39 pulsotypes when a similarity cut-off value of 80 % was implemented. Antibiotic-susceptibility testing against seven different classes of antibiotics showed that 9 % of the isolates were resistant to clindamycin, 23 % were resistant to erythromycin and 4 % showed the macrolide–lincosamide–streptogramin B (MLSB) phenotype. The emergence of tetracycline-resistant strains (37 %) was high when compared with previous reports from Lebanon. This study provided comprehensive evidence of the epidemiology of GAS in Lebanon, highlighting the association between emm types and toxin genes, and providing valuable information about the origin and dissemination of this pathogen.

scholarly journals Streptolysin O and NAD-Glycohydrolase Prevent Phagolysosome Acidification and Promote Group A Streptococcus Survival in Macrophages

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Benedicte Bastiat-Sempe ◽  
John F. Love ◽  
Natalie Lomayesva ◽  
Michael R. Wessels
Keyword(s):  
Streptococcus Pyogenes ◽  
Intracellular Survival ◽  
Streptococcal Toxic Shock Syndrome ◽  
Simple Diffusion ◽  
Content Type ◽  
Nad Glycohydrolase ◽  
Macrophage Phagocytosis ◽  
Streptolysin O ◽  
Invasive Infections ◽  
Group A

ABSTRACTGroup AStreptococcus(GAS,Streptococcus pyogenes) is an ongoing threat to human health as the agent of streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome. In animal models of infection, macrophages have been shown to contribute to host defense against GAS infection. However, as GAS can resist killing by macrophagesin vitroand induce macrophage cell death, it has been suggested that GAS intracellular survival in macrophages may enable persistent infection. Using isogenic mutants, we now show that the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase) mediate GAS intracellular survival and cytotoxicity for macrophages. Unexpectedly, the two toxins did not inhibit fusion of GAS-containing phagosomes with lysosomes but rather prevented phagolysosome acidification. SLO served two essential functions, poration of the phagolysosomal membrane and translocation of NADase into the macrophage cytosol, both of which were necessary for maximal GAS intracellular survival. Whereas NADase delivery to epithelial cells is mediated by SLO secreted from GAS bound to the cell surface, in macrophages, the source of SLO and NADase is GAS contained within phagolysosomes. We found that transfer of NADase from the phagolysosome to the macrophage cytosol occurs not by simple diffusion through SLO pores but rather by a specific translocation mechanism that requires the N-terminal translocation domain of NADase. These results illuminate the mechanisms through which SLO and NADase enable GAS to defeat macrophage-mediated killing and provide new insight into the virulence of a major human pathogen.IMPORTANCEMacrophages constitute an important element of the innate immune response to mucosal pathogens. They ingest and kill microbes by phagocytosis and secrete inflammatory cytokines to recruit and activate other effector cells. Group AStreptococcus(GAS,Streptococcus pyogenes), an important cause of pharyngitis and invasive infections, has been shown to resist killing by macrophages. We find that GAS resistance to macrophage killing depends on the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase). GAS bacteria are internalized by macrophage phagocytosis but resist killing by secreting SLO, which damages the phagolysosome membrane, prevents phagolysosome acidification, and translocates NADase from the phagolysosome into the macrophage cytosol. NADase augments SLO-mediated cytotoxicity by depleting cellular energy stores. These findings may explain the nearly universal production of SLO by GAS clinical isolates and the association of NADase with the global spread of a GAS clone implicated in invasive infections.

scholarly journals Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A Streptococcus

2021 ◽  
Vol 12 ◽  
Author(s):  
Anders F. Johnson ◽  
Christopher N. LaRock
Keyword(s):  
Streptococcus Pyogenes ◽  
Disease Burden ◽  
Group A Streptococcus ◽  
Human Pathogen ◽  
Invasive Infections ◽  
Group A ◽  
Severe Infections ◽  
Treatment Mechanisms ◽  
Antibiotic Failure ◽  
Global Disease Burden

Group A Streptococcus (GAS; Streptococcus pyogenes) is a nearly ubiquitous human pathogen responsible for a significant global disease burden. No vaccine exists, so antibiotics are essential for effective treatment. Despite a lower incidence of antimicrobial resistance than many pathogens, GAS is still a top 10 cause of death due to infections worldwide. The morbidity and mortality are primarily a consequence of the immune sequelae and invasive infections that are difficult to treat with antibiotics. GAS has remained susceptible to penicillin and other β-lactams, despite their widespread use for 80 years. However, the failure of treatment for invasive infections with penicillin has been consistently reported since the introduction of antibiotics, and strains with reduced susceptibility to β-lactams have emerged. Furthermore, isolates responsible for outbreaks of severe infections are increasingly resistant to other antibiotics of choice, such as clindamycin and macrolides. This review focuses on the challenges in the treatment of GAS infection, the mechanisms that contribute to antibiotic failure, and adjunctive therapeutics. Further understanding of these processes will be necessary for improving the treatment of high-risk GAS infections and surveillance for non-susceptible or resistant isolates. These insights will also help guide treatments against other leading pathogens for which conventional antibiotic strategies are increasingly failing.

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