scholarly journals Difference in the structural features of streptococcal M proteins from nephritogenic and rheumatogenic serotypes.

1987 ◽  
Vol 166 (1) ◽  
pp. 151-162 ◽  
Author(s):  
K M Khandke ◽  
T Fairwell ◽  
B N Manjula
Keyword(s):  
Tertiary Structure ◽  
Structural Information ◽  
Gel Filtration ◽  
Structural Features ◽  
Biologically Active ◽  
M Protein ◽  
Acute Glomerulonephritis ◽  
Group A Streptococci ◽  
M Proteins ◽  
Group A

The association of only certain M protein serotypes of group A streptococci with acute glomerulonephritis is very well recognized. Structural information on the M protein, a dimeric alpha-helical coiled-coil molecule, has come so far from three rheumatogenic serotypes, 5, 6, and 24. However, M proteins from the nephritogenic serotypes have not been well characterized. In the present study, we have isolated a biologically active 20,000 Mr pepsin fragment of type 49 M protein (PepM49), a nephritogenic serotype, and purified it to homogeneity using DEAE-Sephadex and gel filtration. The amino acid composition of PepM49 is similar to those of the rheumatogenic M protein serotypes PepM5, PepM6, and PepM24. However, the sequence of the NH2-terminal 60 residues of PepM49 shows little homology to any of these M protein serotypes, although the latter have significant homology among themselves. Nevertheless, PepM49 exhibits a strong heptad periodicity in its nonpolar residues, suggesting its overall conformational similarity with the other M molecules. During the course of the present studies, Moravek et al. (17) reported the NH2-terminal sequence of another M protein serotype, PepM1, which also does not exhibit much homology with the PepM5, PepM6, and PepM24 proteins. Our analysis of this sequence revealed that the PepM1 protein also exhibits a heptad periodicity of the nonpolar amino acids. A closer examination has revealed that the pattern of heptad periodicity in PepM49 and PepM1 proteins is more regular and more similar to each other than has been previously seen for the PepM5, PepM6, and PepM24 proteins. PepM1 is also a nephritogenic serotype. Taken together, these findings indicate an underlying conservation of the tertiary structure of the various M protein serotypes, despite the complexity in their antigenic variation and suggest that the nephritogenic M protein serotypes M1 and M49 may be further apart evolutionarily from the rheumatogenic serotypes 5, 6, and 24. The distinct differences in the structural features of the PepM1 and PepM49 proteins relative to the PepM5, PepM6, and PepM24 proteins are also suggestive of a correlation with the earlier broader classification of the group A streptococci into rheumatogenic and nephritogenic serotypes.

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 Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes

2005 ◽  
Vol 12 (7) ◽  
pp. 833-836 ◽  
Author(s):  
James B. Dale ◽  
Thomas Penfound ◽  
Edna Y. Chiang ◽  
Valerie Long ◽  
Stanford T. Shulman ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Epidemiologic Studies ◽  
M Protein ◽  
Group A Streptococci ◽  
Protein Vaccine ◽  
Amino Terminal ◽  
M Proteins ◽  
Group A ◽  
Clinical Illness

ABSTRACT Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.

scholarly journals Pathogenesis of Group A Streptococcal Infections

2000 ◽  
Vol 13 (3) ◽  
pp. 470-511 ◽  
Author(s):  
Madeleine W. Cunningham
Keyword(s):  
Rheumatic Fever ◽  
Regulatory Networks ◽  
Binding Proteins ◽  
Molecular Mimicry ◽  
Structural Features ◽  
Factor H ◽  
Mucosal Vaccine ◽  
M Protein ◽  
Acute Glomerulonephritis ◽  
Group A

SUMMARY Group A streptococci are model extracellular gram-positive pathogens responsible for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A resurgence of invasive streptococcal diseases and rheumatic fever has appeared in outbreaks over the past 10 years, with a predominant M1 serotype as well as others identified with the outbreaks. emm (M protein) gene sequencing has changed serotyping, and new virulence genes and new virulence regulatory networks have been defined. The emm gene superfamily has expanded to include antiphagocytic molecules and immunoglobulin-binding proteins with common structural features. At least nine superantigens have been characterized, all of which may contribute to toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and throat strains in their epidemiology and genetic makeup. Eleven adhesins have been reported, and surface plasmin-binding proteins have been defined. The strong resistance of the group A streptococcus to phagocytosis is related to factor H and fibrinogen binding by M protein and to disarming complement component C5a by the C5a peptidase. Molecular mimicry appears to play a role in autoimmune mechanisms involved in rheumatic fever, while nephritis strain-associated proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies have focused on recombinant M protein and C5a peptidase vaccines, and mucosal vaccine delivery systems are under investigation.

Experimental nephritis due to type specific streptococci. VI. Further characterization of type 12 nephrotoxin

1969 ◽  
Vol 15 (6) ◽  
pp. 555-561 ◽  
Author(s):  
P. W. Fardy ◽  
B. H. Matheson ◽  
R. W. Reed
Keyword(s):  
Active Material ◽  
Gel Filtration ◽  
Acute Glomerulonephritis ◽  
Acid Hydrolysate ◽  
Culture Filtrates ◽  
Experimental Nephritis ◽  
Chemical Studies ◽  
Group A ◽  
High Voltage Electrophoresis

Additional studies were undertaken on the nature of a nephrotoxic agent found in the culture filtrates of certain group A streptococci. A commercially available dehydrated medium proved satisfactory for the production of the active material. Gel filtration was used to divide polypeptide extracts, prepared from the dialyzable portion of culture filtrates, into two major fractions. One of these, representing the higher molecular weight components, contained most of the nephrotoxic activity as evidenced by the development of hypertension and acute glomerulonephritis in rabbits injected with this fraction.Physical and chemical studies indicated that the active fraction consisted of at least four polypeptide components separable by high voltage electrophoresis on paper. Automatic amino acid analysis of an acid hydrolysate of this fraction revealed 17 different amino acids. Carbohydrate was not detected by anthrone and orcinol tests.No relationship was established between this streptococcal nephrotoxic agent and other streptococcal constituents which have been implicated in acute glomerulonephritis.

scholarly journals New 30-valent M protein-based vaccine evokes cross-opsonic antibodies against non-vaccine serotypes of group A streptococci

Vaccine ◽  
2011 ◽  
Vol 29 (46) ◽  
pp. 8175-8178 ◽  
Author(s):  
James B. Dale ◽  
Thomas A. Penfound ◽  
Edna Y. Chiang ◽  
William J. Walton
Keyword(s):  
M Protein ◽  
Group A Streptococci ◽  
Vaccine Serotypes ◽  
Group A
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