Application of emm Gene Sequencing and T Antigen Serology for Typing Group A Streptococcal Systemic Isolates

1997 ◽  
pp. 307-311 ◽  
Author(s):  
Bernard Beall ◽  
Richard Facklam ◽  
Theresa Hoenes ◽  
Ben Schwartz
Keyword(s):  
Gene Sequencing ◽  
T Antigen ◽  
Group A

scholarly journals Group AStreptococcusT Antigens Have a Highly Conserved Structure Concealed under a Heterogeneous Surface That Has Implications for Vaccine Design

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Paul G. Young ◽  
Jeremy M. Raynes ◽  
Jacelyn M. Loh ◽  
Thomas Proft ◽  
Edward N. Baker ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Sequence Divergence ◽  
Structural Similarity ◽  
T Antigen ◽  
T Antigens ◽  
Content Type ◽  
Group A ◽  
Efficacious Vaccine ◽  
High Level ◽  
Conserved Core

ABSTRACTGroup AStreptococcus(GAS) (Streptococcus pyogenes) is an important human pathogen associated with significant global morbidity and mortality for which there is no safe and efficacious vaccine. The T antigen, a protein that polymerizes to form the backbone of the GAS pilus structure, is a potential vaccine candidate. Previous surveys of theteegene, which encodes the T antigen, have identified 21 differentteetypes and subtypes such that any T antigen-based vaccine must be multivalent and carefully designed to provide broad strain coverage. In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The existence of shared epitopes between T antigens, combined with the remarkably conserved structure and high level of surface sequence divergence, has important implications for the design of multivalent T antigen-based vaccines.

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 THE PROPERTIES OF T ANTIGENS EXTRACTED FROM GROUP A HEMOLYTIC STREPTOCOCCI

1946 ◽  
Vol 84 (5) ◽  
pp. 449-471 ◽  
Author(s):  
Rebecca C. Lancefield ◽  
Vincent P. Dole
Keyword(s):  
Proteolytic Enzymes ◽  
Enzymatic Digestion ◽  
T Antigen ◽  
Soluble Form ◽  
Bacterial Cells ◽  
T Antigens ◽  
Acid Media ◽  
Elementary Analysis ◽  
Group A

1. T antigens of group A hemolytic streptococci have been obtained in soluble form by digestion of the bacterial cells with pepsin or trypsin. Large quantities of this antigen were readily extracted from type 1 strains, whereas only small amounts could be obtained from strains of other types. 2. The T antigen, prepared in this way from a type 1 strain, was partially purified by chemical precipitation and further enzymatic digestion. An active fraction, apparently protein in nature, was separated electrophoretically at pH 7.00. The separated material, pooled and analyzed at the same pH, gave only a single peak. The isoelectric point of this substance was about pH 4.50. An elementary analysis was obtained. Although the T antigen was resistant to digestion with proteolytic enzymes and ribonuclease, it was readily inactivated by heat, especially in acid media and in strong salt solutions. The serological activity of this purified T substance was lost after exposure to ultraviolet radiation. 3. Analysis by means of the ultracentrifuge showed that the material was polydisperse and therefore probably impure. 4. The soluble form of the T substance was active in the precipitin reaction, in the fixation of complement, in inhibition of T agglutination, and as an antigen when injected into rabbits. The antibodies produced did not protect mice against infection with virulent strains of hemolytic streptococci containing the same T antigen. 5. The immunological specificity of T antigen in soluble form is the same as that of the T antigen in the intact streptococcus from which it was derived

scholarly journals VARIATION OCCURRING IN GROUP A STREPTOCOCCI DURING HUMAN INFECTION

1948 ◽  
Vol 87 (6) ◽  
pp. 521-533 ◽  
Author(s):  
Sidney Rothbard ◽  
Robert F. Watson
Keyword(s):  
T Antigen ◽  
Human Infection ◽  
M Protein ◽  
Group A Streptococci ◽  
Upper Respiratory Tract ◽  
Group A ◽  
Normal Human ◽  
Streptococcal Proteinase ◽  
Relationship Of ◽  
Observation Period

A study was made of the variation occurring in group A streptococci during the natural course of infection in man. From 54 patients with 56 different group A streptococcal infections of the upper respiratory tract, 251 strains of streptococci, isolated at weekly intervals following infection, were tested for their capacity to resist the bacteriostatic action of normal human blood. In 52 of the infections the streptococci were of recognized serological types and were also tested for variation in their ability to produce the type-specific M protein antigen. Strains isolated in the 1st week of infection were uniformly highly resistant to bacteriostasis and elaborated large amounts of M substance. In 42 per cent of the 52 infections, strains isolated in the convalescent and carrier stages showed an increasing susceptibility to bacteriostasis correlated with a progressive loss of M substance; whereas in the remaining 58 per cent resistance to bacteriostasis and the capacity to produce M protein were maintained throughout the observation period. In 3 different infections, the streptococci became so degraded that no M protein could be demonstrated in acid extracts of these variants. Concomitantly these strains became highly susceptible to bacteriostasis. Spontaneous reversion did not occur, but serial mouse passage reestablished these functions. These degraded variants had the same T antigen as their respective original strains. No evidence was obtained that variation of group A streptococci in resistance to bacteriostasis or in the ability to produce the type-specific M antigen was associated (a) with the appearance of type-specific bacteriostatic antibodies; (b) with any particular serological type of streptococcus; (c) with the production of streptococcal proteinase which digests the M protein; (d) with the therapeutic administration of sulfadiazine; or (e) with the development of complications. The possible relationship of these observations to the problem of the "dangerous carrier" of group A hemolytic streptococci is discussed.

scholarly journals Type 49 Streptococcus pyogenes: Phage subtypes as epidemiological markers in isolates from skin sepsis and acute glomerulonephritis

1983 ◽  
Vol 91 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Stephen A. Skjold ◽  
Lewis W. Wannamaker ◽  
Dwight R. Johnson ◽  
Harold S. Margolis
Keyword(s):  
Streptococcus Pyogenes ◽  
Skin Lesions ◽  
T Antigen ◽  
M Protein ◽  
Acute Glomerulonephritis ◽  
Group A Streptococci ◽  
Related Strain ◽  
Group A ◽  
Epidemiological Markers

SUMMARYStudies of group A, M type 49 streptococci from England, Trinidad and Alaska indicate that isolates of this serotype often differ with respect to phage subtype from one geographical areato another, but are generally homogeneous in one place at one time. The findings support the conclusion that acute glomerulonephritis can be associated with a variety of phage subtypes of M type 49 streptococci.In outbreaks of skin sepsis without nephritis in England, the phage subtypes of M type 49 streptococci isolated from skin lesions of meat handlers were the same as those recovered from skin lesions of non-meat handlers in the same community.The findings on the Trinidad isolates suggest that M type 49 streptococci of one phage subtype may persist in a population for 9 years and may result in a second outbreak of acute glomerulonephritis.In an Alaska Eskimo population in whom acute glomerulonephritis was occurring, most of the M type 49 isolates available for testing were of a single phage subtype. Equally prevalent in this population were group A streptococci that exhibited the same T antigen as the type 49 isolates but differed in their serum opacity reaction and phage subtype. This apparently related strain was not typable with available M antisera but showed functional evidence of M protein and is probably a new M type.

scholarly journals Cytoplasmic Localization of a Functionally Active Fanconi Anemia Group A–Green Fluorescent Protein Chimera in Human 293 Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3288-3295 ◽  
Author(s):  
Frank A.E. Kruyt ◽  
Quinten Waisfisz ◽  
Lonneke M. Dijkmans ◽  
Mario A.J.A. Hermsen ◽  
Hagop Youssoufian ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Fanconi Anemia ◽  
Fluorescent Protein ◽  
Bone Marrow Failure ◽  
T Antigen ◽  
Cross Linking ◽  
293 Cells ◽  
Group A ◽  
Cytoplasmic Compartment ◽  
Green Fluorescent

Abstract Hypersensitivity to cross-linking agents and predisposition to malignancy are characteristic of the genetically heterogeneous inherited bone marrow failure syndrome, Fanconi anemia (FA). The protein encoded by the recently cloned FA complementation group A gene, FAA, has been expected to localize in the nucleus as based on the presence of sequences homologous to a bipartite nuclear localization signal (NLS) and a leucine repeat motif. In contrast to this expectation, we show here that a functionally active FAA-green fluorescent protein (GFP) hybrid resides in the cytoplasmic compartment of human kidney 293 cells. In accordance with this finding, disruption of the putative NLS by site-directed mutagenesis failed to affect both subcellular localization and the capacity to complement hypersensitivity to the cross-linking agent mitomycin C in FA-A lymphoblasts. Furthermore, the N-terminal part of FAA with the putative NLS at amino acid position 18 to 35 showed no nuclear translocation activity when fused to GFP, while the first 115 N-terminal amino acids appeared to be indispensable for the complementing activity in FA-A cells. Similarly, mutagenesis studies of the putative leucine repeat showed that, even though this region of the protein is important for complementing activity, this activity does not depend on an intact leucine zipper motif. Finally, fusion of the NLS motif derived from the SV40 large T antigen to FAA could not direct the hybrid protein into the nucleus of 293 cells, suggesting that FAA is somehow maintained in the cytoplasm via currently unknown mechanisms. Thus, like the first identified FA protein, FAC, FAA seems to exert its function in the cytoplasmic compartment suggesting FA proteins to be active in a yet to be elucidated cytoplasmic pathway that governs hematopoiesis and protects against genomic instability.

scholarly journals Studies on the cell wall of group A streptococcus, with special reference to the T antigen

1960 ◽  
Vol 15 (5) ◽  
pp. 470-473
Author(s):  
Makoto NAKAZAWA ◽  
Yuya NAKAMURA ◽  
Nobuyuki SAKAI
Keyword(s):  
Cell Wall ◽  
Special Reference ◽  
Group A Streptococcus ◽  
T Antigen ◽  
Group A

scholarly journals Studies on the cell wall of group A streptococcus, with special reference to the T antigen

1959 ◽  
Vol 14 (6) ◽  
pp. 538-541
Author(s):  
Makoto NAKAZAWA ◽  
Yuya NAKAMURA
Keyword(s):  
Cell Wall ◽  
Special Reference ◽  
Group A Streptococcus ◽  
T Antigen ◽  
Group A

scholarly journals Streptococcus pyogenes in the throat: a study in a small population, 1962–1975

1981 ◽  
Vol 87 (1) ◽  
pp. 109-129 ◽  
Author(s):  
R. Edgar Hope-Simpson
Keyword(s):  
Streptococcus Pyogenes ◽  
Respiratory Diseases ◽  
Small Population ◽  
T Antigen ◽  
Simple Estimate ◽  
Practice Population ◽  
Laboratory Surveillance ◽  
Group A ◽  
General Community

SummaryA general practice population of around 6700 was kept under clinical and laboratory surveillance from 1962 to 1975. Illnesses totalled 18703 in three morbidity classes: sore throat (Throats) 4451, acute febrile respiratory diseases (FRD) 4934, acute non-febrile respiratory diseases (Non-FRD) 9318. Specimens were examined for beta-haemolytic streptococci (BHS) from 37·1% of these illnesses: from Throats 33·3%, from FRD 67·8%, from Non-FRD 22·6%, and 515 specimens were collected from a miscellaneous (‘Other’) class consisting of healthy persons and ailments that could not have had a streptococcal component.Strains of BHS were isolated from 7448 specimens as follows: group A (Streptococcus pyogenes) 353, group C 36, group G 15, other groups 274.Group A strains were isolated from specimens at the following rates: Throats 16·7 %, FRD 2·4%, Non-FRD 0·9 %, Other 1·4 %. The last two classes reflect the carrier rate in the general community, which must be deducted to obtain the streptococcal morbidity in the other classes. Carriers thus accounted for 6% of the strains isolated from the Throats class and for 42 % of those from FRD illnesses.No consistent seasonal trend of prevalence was detected. Long-term fluctuations in prevalence over several years affected all groups and most group A serotypes.Serotyping was performed on 304 strains from 1963 to 1975. The commonest types found were T-types 4 and 12 and M-type 12.Immunity against re-infection by identical strains appeared to be fairly strong and also against heterotypic strains that shared a T-antigen, but little protection was conferred against re-infection by group A strains with no shared M- or T-antigen. R-28 antigen is considered here as a marker epidemiologically equivalent to an M-antigen.Epidemicity, as measured by a simple estimate of aggregation, appeared to be low and there were differences between and within serotypes.The infecting organism appeared to linger in the pharynx, sometimes for several months, after a streptococcal illness.

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