Joseph J. Ferretti*†, William M. McShan*, Dragana Ajdic*, Dragutin J. Savic*, Gorana Savic*, Kevin Lyon*, Charles Primeaux*, Steven Sezate*, Alexander N. Suvorov*‡, Steve Kenton§, Hong Shing Lai§, Shao Ping Lin§, Yudong Qian§, Hong Gui Jia§, Fares Z. Najar§, Qun Ren§, Hua Zhu§, Lin Song§, Jim White§, Xiling Yuan§, Sandra W.Clifton§¶, Bruce A. Roe§, and Robert McLaughlin*
*Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190; and §Department of Biochemistry, University of Oklahoma, Norman, OK 73019 Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved January 26, 2001 (received for review November 27, 2000)
The 1,852,442-bpsequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately onethird of these genes have no identiﬁable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety ofhuman disease than any other bacterial species, more than 40 putative virulenceassociated genes have been identiﬁed. Additional genes have been identiﬁed that encode proteins likely associated with microbial ‘‘molecular mimicry’’ of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is alsopresent, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.
treptococcus pyogenes, also known as group Astreptococci (GAS), is a strict human pathogen, and no other known reservoir or species is affected by diseases unique to this organism. As a member of the low G C% family of Grampositive bacteria, this pathogen is responsible for a wide variety of disease, including pharyngitis (streptococcal sore throat), scarlet fever, impetigo, erysipelas, cellulitis, septicemia, toxic shock syndrome, necrotizingfasciitis (flesh-eating disease) and the sequelae, rheumatic fever and acute glomerulonephritis. Genetic variability is known to occur, as evidenced by the appearance of strains associated with outbreaks of infection such as necrotizing fasciitis, toxic shock syndrome, and rheumatic fever (1–3). The GAS are remarkable for the number of extracellular proteins produced, many of which have beendemonstrated to increase the virulence of the organism. These proteins often trigger a severe nonspecific immunological response in the human host. S. pyogenes strains are grouped into two classes on the basis of postinfectious sequelae associated with each strain, class I responsible for rheumatic fever and class II responsible for acute glomerulonephritis. Class I organisms, besides being associated withpoststreptococcal rheumatic fever, possess an immunodeterminant contained in a surface-exposed conserved (C repeat domain) region of the M protein (class I M protein) that is lacking in class II proteins (4). In this report, we present the complete genomic sequence of a class I strain of S. pyogenes.
brary was constructed from Sau3aI partially digested genomic DNA and cloned into thereplacement vector, BlueSTAR (Novagen). End sequences from clones were used in determining contig linkage for gap closure and final genome linkage verification. All sequences were assembled by using the PHRED PHRAP CONSED software package (http: bozeman. mbt.washington.edu) (6, 7). Gap closure was accomplished through a primer-walking plasmid template and direct sequencing of combinatorial PCR...