Pyogenic Group Streptococcus pyogenes

Streptococcus pyogenes, the group A streptococcus (GAS), is a strict human pathogen responsible for a wide variety of diseases, ranging from acute infections such as pharyngitis, scarlet fever, and erysipelas to severe invasive infections such as necrotizing fasciitis (flesh-eating disease) and streptococcal toxic shock syndrome, as well as the sequelae of rheumatic fever and acute glomerulonephritis. This organism has been divided into over 150 distinct M types based on serological differences found in a surface protein known as the M protein (specified by the emm gene). The genome sequences of seven different strains of GAS have been completed, including Ml [5], M3 (two strains) [6, 7], M5 ( S_pyogenes/), M6 [8], M18 [9], and M49 (McShan, personal communication) strains (Table 8.1). The average G+C content ranged from 38.4% to 38.7 % and the genome size from 1.84 Mbp to 1.90 Mbp. A prominent feature of the genomes is the presence of mobile genetic elements; i.e., bacteriophage genomes, insertion sequences (IS), and other transposase-containing elements. Bacteriophages are ubiquitous in GAS genomes [10], which contain between two and six different integrated bacteriophage genomes, accounting for up to 12% of the GAS genome (M6). The presence of these phage genomes accounts for the major differences in gene content and size observed between GAS strains, with most core and functional categories of genes being highly conserved.

The genomes of the six different M-type strains for which complete sequences are available all contained six rRNA operons. A characteristic of these genomes is that most genes (approx. 75%) are located on the leading rather than the lagging strand of replication. Another feature is that gene order and chromosome organization of the various GAS genomes is generally conserved. Nevertheless, variation here also occurs, as evidenced by large chromosome inversions found in M3 and M5 strains. Nakagawa and colleagues [7] showed that large chromosome rearrangements were found in 65% of M3 strains analyzed in Japan after 1990, but only 25% of strains analyzed before 1985. These recombinations occurred across the replication axis and between homologous bacterial chromosome and prophage sequences, resulting in gross changes in gene order (Fig. 8.1). The alignment of six different GAS genomes is also shown in Fig. 8.1, where it can be seen for the most part that gene order and orientation are highly preserved. Note that significant inversions are present in both the M3 (SSI-1) and M5 genomes.

Genetic diversity has been described in GAS strains as ascertained by single nucleotide polymorphism analysis, whole genome polymerase chain reaction (PCR) scanning, and DNA-DNA microarray analysis [12]. Allelic variation and polymorphisms are particularly common among the GAS virulence genes [13], as

0 0

Post a comment