VM-LC T2 Streptococcus pyogenes by Anis.Z Azahan

Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates.
http://www.sciencedirect.com/science/article/pii/S0264410X16300706

2) Streptococcus pyogenes causing toxic-shock-like syndrome and other invasive diseases: clonal diversity and pyrogenic exotoxin expression.
Genetic diversity and relationships among 108 isolates of the bacterium Streptococcus pyogenes recently recovered from patients in the United States with toxic-shock-like syndrome or other invasive diseases were estimated by multilocus enzyme electrophoresis. Thirty-three electrophoretic types (ETs), representing distinctive multilocus clonal genotypes, were identified, but nearly half the disease episodes, including more than two-thirds of the cases of toxic-shock-like syndrome, were caused by strains of two related clones (ET 1 and ET 2). These two clones were also represented by recent pathogenic European isolates. A previous report of a relatively high frequency of expression of exotoxin A among isolates recovered from toxic-shock-like syndrome patients in the United States was confirmed; and the demonstration of this association both within clones and among distantly related clones supports the hypothesis that exotoxin A is a causal factor in pathogenesis of this disease. Near identity of the nucleotide sequences of the exotoxin A structural gene of six isolates of five ETs in diverse phylogenetic lineages was interpreted as evidence that the gene has been horizontally distributed among clones, presumably by bacteriophage-mediated transfer.
http://www.pnas.org/content/88/7/2668.short

3) Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome.

Toxic shock-like syndrome (TSLS) is characterized by hypotension or shock, fever, multiorgan system involvement, and a concurrent group A streptococcal infection. We analyzed 34 streptococcal strains isolated from patients with clinically well-documented TSLS for their pyrogenic toxin profiles and M-protein types. Although strains of nine different M types were represented in the sample, 74% of the isolates were of either M type 1 or 3. It was determined that 53% produced streptococcal pyrogenic exotoxin type A under in vitro growth conditions and that 85% contained the gene encoding this toxin. These values are in contrast to the published value of 15% for the incidence of this gene in a sample of general group A streptococcal isolates. As has been found with all group A streptococci examined to date, regardless of disease association, 100% of TSLS-associated isolates contained the gene encoding pyrogenic exotoxin type B. This toxin was detectably produced by 59% of isolates. The gene encoding pyrogenic toxin type C was found in only 21% of isolates. We conclude that the pyrogenic exotoxin type A gene is associated with group A streptococcal strains isolated from patients with TSLS and may play a causative role in this illness. However, other factors are also likely to be important, since not all strains from patients with TSLS contained the A toxin gene.
http://jcm.asm.org/content/29/8/1562.short