scholarly journals Characterization ofsilin Invasive Group A and G Streptococci: Antibodies against Bacterial Pheromone Peptide SilCR Result in Severe Infection

2013 ◽  
Vol 81 (11) ◽  
pp. 4121-4127 ◽  
Author(s):  
Ayelet Michael-Gayego ◽  
Mary Dan-Goor ◽  
Joseph Jaffe ◽  
Carlos Hidalgo-Grass ◽  
Allon E. Moses
Keyword(s):  
Murine Model ◽  
Group A Streptococcus ◽  
Severe Infection ◽  
Gene Arrangement ◽  
Severe Illness ◽  
Virulence Attenuation ◽  
Bacterial Quorum Sensing ◽  
Invasive Infections ◽  
Group A ◽  
Bacterial Quorum

ABSTRACTGroup G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus,sil, was identified in GAS.silencodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found thatsilis present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that containedsilexpressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that thesillocus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.

Diverse disease processes of group A Streptococcus infection including severe invasive infections among members of a family

2021 ◽  
Vol 14 (4) ◽  
pp. e241339
Author(s):  
Kaori Amari ◽  
Masaki Tago ◽  
Naoko E Katsuki ◽  
Shu-ichi Yamashita
Keyword(s):  
Septic Shock ◽  
Distress Syndrome ◽  
Clinical Course ◽  
Group A Streptococcus ◽  
Bloody Stool ◽  
Laryngeal Oedema ◽  
Invasive Infections ◽  
Group A ◽  
The Right ◽  
Close Contacts

We herein report three cases of group A Streptococcus (GAS) infection in a family. Patient 1, a 50-year-old woman, was transferred to our hospital in shock with acute respiratory distress syndrome, swelling in the right neck and erythemata on both lower extremities. She required intubation because of laryngeal oedema. At the same time, patient 2, a 48-year-old man, was admitted because of septic shock, pneumonia and a pulmonary abscess. Five days later, patient 3, a 91-year-old woman, visited our clinic with bloody stool. All three patients were cured by antibiotics, and GAS was detected by specimen cultures. During these patients’ clinical course, an 84-year-old woman was found dead at home after having been diagnosed with type A influenza. All four patients lived in the same apartment. The GAS genotypes detected in the first three patients were identical. When treating patients with GAS, appropriate management of close contacts is mandatory.

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 Identification of Group A Streptococcus Antigenic Determinants Upregulated In Vivo

2005 ◽  
Vol 73 (9) ◽  
pp. 6026-6038 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Dennis G. Cvitkovitch ◽  
Peter Chang ◽  
Darrin J. Bast ◽  
Martin Handfield ◽  
...  
Keyword(s):  
Murine Model ◽  
Vibrio Vulnificus ◽  
Group A Streptococcus ◽  
Hypothetical Protein ◽  
Invasive Disease ◽  
Antigenic Determinants ◽  
Expression Library ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products—a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus—were upregulated in vivo, suggesting that these genes play a role during invasive disease.

scholarly journals Identification and Characterization of an Antigen I/II Family Protein Produced by Group A Streptococcus

2006 ◽  
Vol 74 (7) ◽  
pp. 4200-4213 ◽  
Author(s):  
Shizhen Zhang ◽  
Nicole M. Green ◽  
Izabela Sitkiewicz ◽  
Rance B. LeFebvre ◽  
James M. Musser
Keyword(s):  
Cell Surface ◽  
Group A Streptococcus ◽  
Bacterial Pathogen ◽  
Severe Infection ◽  
Genomic Islands ◽  
Oral Streptococci ◽  
Group B Streptococci ◽  
Gram Positive ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) is a gram-positive human bacterial pathogen that causes infections ranging in severity from pharyngitis to life-threatening invasive disease, such as necrotizing fasciitis. Serotype M28 strains are consistently isolated from invasive infections, particularly puerperal sepsis, a severe infection that occurs during or after childbirth. We recently sequenced the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign genetic element designated region of difference 2 (RD2). RD2 is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections. RD2 encodes seven proteins with conventional gram-positive secretion signal sequences, six of which have not been characterized. Herein, we report that one of these six proteins (M28_Spy1325; Spy1325) is a member of the antigen I/II family of cell surface-anchored molecules produced by oral streptococci. PCR and DNA sequence analysis found that Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in vitro, and Spy1325 protein was present in culture supernatants and on the GAS cell surface. Western immunoblotting and enzyme-linked immunosorbent assays indicated that Spy1325 was produced by GAS in infected mice and humans. Importantly, the immunization of mice with recombinant Spy1325 fragments conferred protection against GAS-mediated mortality. Similar to other antigen I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and oral streptococci.

scholarly journals 215. Invasive Group A Streptococcus-Associated Hospitalizations and Risk Factors for In-Hospital Mortality Among Adults in California, 2000–2016

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S126-S127
Author(s):  
Ellora Karmarkar ◽  
Seema Jain ◽  
Gail L Sondermeyer Cooksey ◽  
Jennifer Myers ◽  
Amanda Kamali
Keyword(s):  
Risk Factors ◽  
Group A Streptococcus ◽  
Continuous Variable ◽  
Incidence Rates ◽  
Severe Illness ◽  
Hospital Death ◽  
Discharge Data ◽  
Invasive Group ◽  
Group A ◽  
Race Ethnicity

Abstract Background Invasive group A Streptococcus (iGAS) causes severe illness and death but is not vaccine preventable or nationally notifiable. We describe the epidemiology of adult patients hospitalized with iGAS in California and risk factors for in-hospital death. Methods Using 2000–2016 California hospital discharge data, we extracted records for adults (≥18 years) with ≥1 group A Streptococcus (GAS)-associated International Classification of Diseases, Ninth or Tenth Revision discharge diagnosis code (e.g., unspecified GAS; GAS-specific pharyngitis, pneumonia, and sepsis) or known GAS-associated syndromes (e.g., acute rheumatic fever, erysipelas, scarlet fever). To identify patients hospitalized with iGAS, we selected extracted records that also had codes consistent with invasive disease (e.g., sepsis, pneumonia, intubation, or central line placement). We calculated iGAS-associated hospitalization incidence rates per 100,000 population and described patient demographics and comorbidities. We calculated the odds of in-hospital death using multivariable logistic regression (P < 0.05). Results During 2000–2016 in California, 37,532 adults were hospitalized with iGAS; 1,045 (3%) died in-hospital. Mean annual hospitalization incidence was 9.4/100,000 population, and was highest (16.3/100,000) in 2016 (Figure 1). Most patients were male (56%), aged 40–65 (45%) or ≥65 (28%) years, and white (60%); 18% were immunocompromised. The percent of patients who died in-hospital increased with age and was highest among those with comorbidities such as malnutrition, cardiovascular disease (CVD), and chronic kidney disease (CKD) (Figure 2). In a multivariable model including age as a continuous variable, sex, and race-ethnicity, the odds of in-hospital death was significantly increased for patients with diagnosis codes for malnutrition, liver disease, CVD, immunosuppression, and CKD (Figure 2); within the race/ethnicity variable Asian/Pacific Islander patients had a higher odds of death compared with white patients. Conclusion Hospitalization and subsequent in-hospital death due to iGAS is substantial in California. Adults with iGAS who have specific comorbidities are at greater risk for death when hospitalized with iGAS. Disclosures All authors: No reported disclosures.

scholarly journals Functional analysis of a group A streptococcal glycoside hydrolase Spy1600 from family 84 reveals it is a β-N-acetylglucosaminidase and not a hyaluronidase

2006 ◽  
Vol 399 (2) ◽  
pp. 241-247 ◽  
Author(s):  
William L. Sheldon ◽  
Matthew S. Macauley ◽  
Edward J. Taylor ◽  
Charlotte E. Robinson ◽  
Simon J. Charnock ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Catalytic Mechanism ◽  
Group A Streptococcus ◽  
Competitive Inhibitor ◽  
Glycoside Hydrolases ◽  
Glycoside Hydrolase Family ◽  
Toxic Shock ◽  
Nmr Studies ◽  
Invasive Infections ◽  
Group A

Group A streptococcus (Streptococcus pyogenes) is the causative agent of severe invasive infections such as necrotizing fasciitis (the so-called ‘flesh eating disease’) and toxic-shock syndrome. Spy1600, a glycoside hydrolase from family 84 of the large superfamily of glycoside hydrolases, has been proposed to be a virulence factor. In the present study we show that Spy1600 has no activity toward galactosaminides or hyaluronan, but does remove β-O-linked N-acetylglucosamine from mammalian glycoproteins – an observation consistent with the inclusion of eukaryotic O-glycoprotein 2-acetamido-2-deoxy-β-D-glucopyranosidases within glycoside hydrolase family 84. Proton NMR studies, structure–reactivity studies for a series of fluorinated analogues and analysis of 1,2-dideoxy-2′-methyl-α-D-glucopyranoso-[2,1-d]-Δ2′-thiazoline as a competitive inhibitor reveals that Spy1600 uses a double-displacement mechanism involving substrate-assisted catalysis. Family 84 glycoside hydrolases are therefore comprised of both prokaryotic and eukaryotic β-N-acetylglucosaminidases using a conserved catalytic mechanism involving substrate-assisted catalysis. Since these enzymes do not have detectable hyaluronidase activity, many family 84 glycoside hydrolases are most likely incorrectly annotated as hyaluronidases.

scholarly journals Human Disease Isolates of Serotype M4 and M22 Group A Streptococcus Lack Genes Required for Hyaluronic Acid Capsule Biosynthesis

mBio ◽  
2012 ◽  
Vol 3 (6) ◽  
Author(s):  
Anthony R. Flores ◽  
Brittany E. Jewell ◽  
Nahuel Fittipaldi ◽  
Stephen B. Beres ◽  
James M. Musser
Keyword(s):  
Hyaluronic Acid ◽  
Virulence Factor ◽  
Group A Streptococcus ◽  
Ex Vivo ◽  
Upper Respiratory Tract ◽  
Major Virulence Factor ◽  
Invasive Infections ◽  
Group A ◽  
Human Infections ◽  
Hyaluronic Acid Capsule

ABSTRACTGroup A streptococcus (GAS) causes human pharyngitis and invasive infections and frequently colonizes individuals asymptomatically. Many lines of evidence generated over decades have shown that the hyaluronic acid capsule is a major virulence factor contributing to these infections. While conducting a whole-genome analysis of thein vivomolecular genetic changes that occur in GAS during longitudinal human pharyngeal interaction, we discovered that serotypes M4 and M22 GAS strains lack thehasABCgenes necessary for hyaluronic acid capsule biosynthesis. Using targeted PCR, we found that all 491 temporally and geographically diverse disease isolates of these two serotypes studied lack thehasABCgenes. Consistent with the lack of capsule synthesis genes, none of the strains produced detectable hyaluronic acid. Despite the lack of a hyaluronic acid capsule, all strains tested multiplied extensivelyex vivoin human blood. Thus, counter to the prevailing concept in GAS pathogenesis research, strains of these two serotypes do not require hyaluronic acid to colonize the upper respiratory tract or cause abundant mucosal or invasive human infections. We speculate that serotype M4 and M22 GAS have alternative, compensatory mechanisms that promote virulence.IMPORTANCEA century of study of the antiphagocytic hyaluronic acid capsule made by group A streptococcus has led to the concept that it is a major virulence factor contributing to human pharyngeal and invasive infections. However, the discovery that some strains that cause abundant human infections lack hyaluronic acid biosynthetic genes and fail to produce this capsule provides a new stimulus for research designed to understand the group A streptococcus factors contributing to pharyngeal infection and invasive disease episodes.

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