scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

scholarly journals Invasive group A Streptococcus disease in Australian children: 2016 to 2018 – a descriptive cohort study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jane Oliver ◽  
◽  
Elise Thielemans ◽  
Alissa McMinn ◽  
Ciara Baker ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Incidence Rates ◽  
Surveillance Systems ◽  
Invasive Group ◽  
Australian State ◽  
Life Threatening ◽  
Group A

Abstract Objectives Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. Methods IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. Results A total of 181 patients were identified, with most (115, 63.5%) <5 years old. The mean annual minimum incidence rate was 1.6 (95% confidence interval: 1.1–2.3) per 100,000 children across the study period. An epidemiological correlation with the seasonal burden of influenza was noted. Contact prophylaxis was not consistently offered. Of 96 patients with emm-typing results available, 72.9% showed emm-1, −4 or − 12. Conclusions Robust surveillance systems and cohesive patient management guidelines are needed. Making iGAS disease nationally notifiable would help facilitate this. Influenza vaccination may contribute to reducing seasonal increases in iGAS incidence. The burden of disease emphasises the need for ongoing progress in GAS vaccine development.

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 Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems Against Group A Streptococcus

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 58 ◽  
Author(s):  
Azuar ◽  
Jin ◽  
Mukaida ◽  
Hussein ◽  
Toth ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Group A Streptococcus ◽  
Delivery Systems ◽  
Peptide Vaccines ◽  
Peptide Epitope ◽  
The Public ◽  
Life Threatening ◽  
Group A ◽  
Preclinical And Clinical Studies ◽  
Traditional Approaches

Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.

scholarly journals A multivalent T-antigen-based vaccine for Group A Streptococcus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacelyn M. S. Loh ◽  
Tania Rivera-Hernandez ◽  
Reuben McGregor ◽  
Adrina Hema J. Khemlani ◽  
Mei Lin Tay ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Recombinant Proteins ◽  
Group A Streptococcus ◽  
Vaccine Coverage ◽  
Protective Efficacy ◽  
Invasive Disease ◽  
T Antigen ◽  
Major Protein ◽  
T Antigens ◽  
Group A

AbstractPili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against GAS infections and the T-antigen represents an attractive target for vaccination. We have generated a multivalent vaccine called TeeVax1, a recombinant protein that consists of a fusion of six T-antigen domains. Vaccination with TeeVax1 produces opsonophagocytic antibodies in rabbits and confers protective efficacy in mice against invasive disease. Two further recombinant proteins, TeeVax2 and TeeVax3 were constructed to cover 12 additional T-antigens. Combining TeeVax1–3 produced a robust antibody response in rabbits that was cross-reactive to a full panel of 21 T-antigens, expected to provide over 95% vaccine coverage. These results demonstrate the potential for a T-antigen-based vaccine to prevent GAS infections.

scholarly journals The Shock of Strep: Rapid Deaths Due to Group a Streptococcus

2018 ◽  
Vol 8 (1) ◽  
pp. 136-149 ◽  
Author(s):  
Katrina M. Thompson ◽  
Alana K. Sterkel ◽  
Joseph A. McBride ◽  
Robert F. Corliss
Keyword(s):  
Streptococcus Pyogenes ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Significant Morbidity ◽  
Invasive Group ◽  
Life Threatening ◽  
Group A ◽  
Severe Infections ◽  
Microscopic Findings ◽  
Positive Coccus

Streptococcus pyogenes, also known as group A beta-hemolytic strep, is a Gram positive coccus responsible for several million infections every year. The types of infections vary widely from pharyngitis to myositis, but all can advance to severe life threatening invasive disease. Of those infected, approximately 1100 to 1600 people die each year due to invasive disease. Why certain individuals contract severe infections is not known, but many strains of Streptococcus pyogenes are known to produce toxins and superantigens. Invasive Streptococcus pyogenes infections have been shown to cause significant morbidity and rapid mortality. In many cases, patients expire before full antemortem testing can be performed, causing physicians and families to look to forensic pathologists for answers. Understanding the pathogenesis of invasive group A strep infections, relevant gross and microscopic findings, and proper culturing techniques is critical for forensic pathologists to diagnosis this condition and assist in the education and protection of the communities they serve.

Etiology, clinical presentation, laboratory diagnostics, pathogenesis of impetigo and treatment methods

2020 ◽  
pp. 64-70
Author(s):  
Anastasiya Laknitskaya
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Diseases ◽  
Group A Streptococcus ◽  
Antibiotic Sensitivity ◽  
Antioxidant Defense System ◽  
Laboratory Diagnostics ◽  
Treatment Methods ◽  
Group A ◽  
The Individual

Currently, one of the priority medical and social problems is the optimization of treatment methods for pyoderma associated with Streptococcus pyogenes — group A streptococcus (GAS). To date, the proportion of pyoderma, the etiological factor of which is Streptococcus pyogenes, is about 6 % of all skin diseases and is in the range from 17.9 to 43.9 % of all dermatoses. Role of the bacterial factor in the development of streptococcal pyoderma is obvious. Traditional treatment complex includes antibacterial drugs selected individually, taking into account the antibiotic sensitivity of pathognomonic bacteria, and it is not always effective. Currently implemented immunocorrection methods often do not take into account specific immunological features of the disease, the individual, and the fact that the skin performs the function of not only a mechanical barrier, but it is also an immunocompetent organ. Such an approach makes it necessary to conduct additional studies clarifying the role of factors of innate and adaptive immunity, intercellular mediators and antioxidant defense system, that allow to optimize the treatment of this pathology.

scholarly journals Molecular Epidemiology of Group A Streptococcus Infections in The Gambia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 124
Author(s):  
Sona Jabang ◽  
Annette Erhart ◽  
Saffiatou Darboe ◽  
Aru-Kumba Baldeh ◽  
Valerie Delforge ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Epidemiological Data ◽  
The Gambia ◽  
Strain Diversity ◽  
Group A ◽  
Considerable Strain

Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.

scholarly journals Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Mussap ◽  
Vassilios Fanos
Keyword(s):  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Patient Specific ◽  
Wide Range ◽  
Life Threatening ◽  
The Individual ◽  
Host Metabolism

Abstract Human Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection activates a complex interaction host/virus, leading to the reprogramming of the host metabolism aimed at the energy supply for viral replication. Alterations of the host metabolic homeostasis strongly influence the immune response to SARS-CoV-2, forming the basis of a wide range of outcomes, from the asymptomatic infection to the onset of COVID-19 and up to life-threatening acute respiratory distress syndrome, vascular dysfunction, multiple organ failure, and death. Deciphering the molecular mechanisms associated with the individual susceptibility to SARS-CoV-2 infection calls for a system biology approach; this strategy can address multiple goals, including which patients will respond effectively to the therapeutic treatment. The power of metabolomics lies in the ability to recognize endogenous and exogenous metabolites within a biological sample, measuring their concentration, and identifying perturbations of biochemical pathways associated with qualitative and quantitative metabolic changes. Over the last year, a limited number of metabolomics- and lipidomics-based clinical studies in COVID-19 patients have been published and are discussed in this review. Remarkable alterations in the lipid and amino acid metabolism depict the molecular phenotype of subjects infected by SARS-CoV-2; notably, structural and functional data on the lipids-virus interaction may open new perspectives on targeted therapeutic interventions. Several limitations affect most metabolomics-based studies, slowing the routine application of metabolomics. However, moving metabolomics from bench to bedside cannot imply the mere determination of a given metabolite panel; rather, slotting metabolomics into clinical practice requires the conversion of metabolic patient-specific data into actionable clinical applications.

scholarly journals Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013

2015 ◽  
Vol 54 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Karen Rudolph ◽  
Michael G. Bruce ◽  
Dana Bruden ◽  
Tammy Zulz ◽  
Alisa Reasonover ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Case Fatality ◽  
Invasive Disease ◽  
Population Based ◽  
The Arctic ◽  
Surveillance Program ◽  
Bacterial Disease ◽  
Invasive Group ◽  
Laboratory Surveillance ◽  
Group A

The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n= 8), 5.8% (n= 20), and 1.2% (n= 4) of the isolates, respectively. A total of 51emmtypes were identified, of whichemm1 (11.1%) was the most prevalent, followed byemm82 (8.8%),emm49 (7.8%),emm12 andemm3 (6.6% each),emm89 (6.2%),emm108 (5.5%),emm28 (4.7%),emm92 (4%), andemm41 (3.8%). The five most commonemmtypes accounted for 41% of isolates. Theemmtypes in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.

Sign in / Sign up

Export Citation Format

Share Document