Protective immunity to the group A Streptococcus may be only strain specific

Malmanche, de; Dr, Martin

doi:10.1007/bf00196680

Cited by 43 publications

(28 citation statements)

References 20 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The N-terminal variable region of M protein is the portion of the molecule against which type-specific immunity is generated (7). Amino acid sequence variation in this region has been identified among isolates of the same M protein serotype (19,33,34) and has been associated with variation in opsonophagocytosis and killing of GAS by human PMNs (35)(36)(37)(38).…”

Section: Resultsmentioning

confidence: 99%

“…This 4-aa duplication conferred altered immune recognition to M protein. This fact, together with the observation of extreme underrepresentation of synonymous (silent) nucleotide changes in M protein in natural populations (19,33,34), rapid change in M protein structure in epidemiologically linked patients (41,42), and ability of sequence changes in the N terminus of the M protein to alter the efficiency of phagocytosis and killing of GAS by human PMNs (35)(36)(37)(38), strongly suggests that the Emm3.2 variant rose to prominence as a consequence of host selective pressure rather than by chance alone. Inasmuch as GAS initially interacts with many hosts in the oral cavity and epithelial surfaces in the posterior pharynx, we believe that the selection occurs in the upper respiratory tract.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Beres

Sylva

Sturdevant

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

120

115

View full text Add to dashboard Cite

Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n ‫؍‬ 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics.population genetics ͉ evolution ͉ phage ͉ subclone

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Beres

Sylva

Sturdevant

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

120

115

View full text Add to dashboard Cite

show abstract

“…Moreover, identical strains have also accounted for less serious infections, such as pharyngitis, cellulitis, and even asymptomatic carriage. Whether or not the high prevalence and persistence of such strains are due to an absence of protective immunity in a significant portion of the human population or to changes in the protective epitopes of the organism remains unclear (5,7). Previous studies have shown that subtle differences, e.g., in the surface structure of the M1 protein, render some strains resistant to immune sera.…”

mentioning

confidence: 99%

drs (Distantly Related sic ) Gene Polymorphisms among emm12 -Type Streptococcus pyogenes Isolates

et al. 2003

View full text Add to dashboard Cite

Twenty-eight emm12-type Streptococcus pyogenes isolates from patients with invasive and noninvasive infections or from asymptomatic carriers were genetically typed. Sequencing of drs (distantly related sic [streptococcal inhibitor of complement]) genes identified two novel alleles and revealed a polymorphism for drs similar to that of sic. No association was observed between the five different drs alleles and the five restriction patterns of the vir regulon for the isolates studied. These data suggest that drs sequencing may be useful for further differentiation of S. pyogenes isolates with emm12 and identical vir regulon restriction patterns.The worldwide emergence of invasive Streptococcus pyogenes infections since the first description of streptococcal toxic shock syndrome almost 20 years ago (4) and the persistence of these infections are still unexplained (22). Particularly, isolates with prevalent emm types, largely emm1, followed by emm3, emm28, and emm12, have the ability to persist in the human environment for long periods, despite the fact that the world's population has likely been exposed to these strains on numerous occasions. Results of established molecular typing methods, including restriction fragment length polymorphism pattern analysis, random amplified polymorphic DNA (RAPD) analysis, and multilocus sequence typing, have revealed only very few individual clones of invasive emm1-type isolates over the past 2 decades (6, 17). Moreover, identical strains have also accounted for less serious infections, such as pharyngitis, cellulitis, and even asymptomatic carriage. Whether or not the high prevalence and persistence of such strains are due to an absence of protective immunity in a significant portion of the human population or to changes in the protective epitopes of the organism remains unclear (5, 7). Previous studies have shown that subtle differences, e.g., in the surface structure of the M1 protein, render some strains resistant to immune sera. Moreover, it has been postulated that natural selection on human mucosal surfaces for variants of the sic gene encoding the streptococcal inhibitor of complement (SIC) contributes to the emergence or reemergence of emm1-type S. pyogenes (13). Sequencing of the highly polymorphic sic genes of 1,132 of emm1-type S. pyogenes isolates derived from global sources has previously shown a high level of allelic diversity, with 220 distinct genes coding for 215 SIC protein variants. This polymorphism of sic has been applied to genetic subtyping of S. pyogenes isolates with emm1 and thus unambiguously differentiated isolates from temporally clustered invasive disease episodes (11). While the sic gene has previously been detected only within the vir(mga) regulon of all S. pyogenes strains harboring emm1 and outside the vir(mga) regulon of S. pyogenes strains with emm57 (1, 10), in a most recent study on S. pyogenes isolates from Japan, the presence of the sic gene was also reported with different frequencies for isolates harboring either emm2, emm4, emm12, emm28...

show abstract

“…The amino acid sequence of the amino terminus of the M protein is responsible for the serotype of the organism, with at least 80 distinct serotypes having been defined (19). Antibodies directed to the M protein opsonize streptococci in the presence of neutrophils; however, these antibodies are serotype specific and generally only opsonize the homologous GAS isolate (1,2,10,13,14,21).…”

mentioning

confidence: 99%

Protective and Nonprotective Epitopes from Amino Termini of M Proteins from Australian Aboriginal Isolates and Reference Strains of Group A Streptococci

et al. 2000

View full text Add to dashboard Cite

The M protein is the primary vaccine candidate to prevent group A streptococcal (GAS) infection and the subsequent development of rheumatic fever (RF). However, the large number of serotypes have made it difficult to design a vaccine against all strains. We have taken an approach of identifying amino-terminal M protein epitopes from GAS isolates that are highly prevalent in GAS-endemic populations within the Northern Territory (NT) of Australia. Australian Aboriginals in the NT experience the highest incidence of RF worldwide. To develop a vaccine for this population, 39 peptides were synthesized, representing the amino-terminal region of the M protein from endemic GAS. Mice immunized with these peptides covalently linked to tetanus toxoid and emulsified in complete Freund's adjuvant raised high-titer antibodies. Over half of these sera reduced bacterial colony counts by >80% against the homologous isolate of GAS. Seven of the peptide antisera also cross-reacted with at least three other heterologous peptides by enzyme-linked immunosorbent assay. Antiserum to one peptide, BSA10 1-28 , could recognize six other peptides, and five of these peptides could inhibit opsonization mediated by BSA10 1-28 antiserum. Cross-opsonization studies showed that six of these sera could opsonize at least one heterologous isolate of GAS. These data reveal vaccine candidates specific to a GASendemic area and show the potential of some to cross-opsonize multiple isolates of GAS. This information will be critical when considering which epitopes may be useful in a multiepitope vaccine to prevent GAS infection.

show abstract

Protective immunity to the group A Streptococcus may be only strain specific

Cited by 43 publications

References 20 publications

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

drs (Distantly Related sic ) Gene Polymorphisms among emm12 -Type Streptococcus pyogenes Isolates

Protective and Nonprotective Epitopes from Amino Termini of M Proteins from Australian Aboriginal Isolates and Reference Strains of Group A Streptococci

Contact Info

Product

Resources

About