The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram
-positive pathogen, has been determined and contains 1,752 predicted protei
n-encoding genes, Approximately one-third of these genes have no identifiab
le function, with the remainder falling into previously characterized categ
ories of known microbial function. Consistent with the observation that S,
pyogenes is responsible for a wider variety of human disease than any other
bacterial species, more than 40 putative virulence-associated genes have b
een identified. Additional genes have been identified that encode proteins
likely associated with microbial "molecular mimicry" of host characteristic
s and involved in rheumatic fever or acute glomerulonephritis, The complete
or partial sequence of four different bacteriophage genomes is also presen
t, with each containing genes for one or more previously undiscovered super
antigen-like proteins. These prophage-associated genes encode at least six
potential virulence factors, emphasizing the importance of bacteriophages i
n horizontal gene transfer and a possible mechanism for generating new stra
ins with increased pathogenic potential.