GENOMICS: Phage Genes Make Bad Bug Worse
Group A “Streptococcus” (GAS) bacteria have acquired virulence factors from bacteriophage, according to Stephen Beres and James Musser of Rocky Mountain National Laboratories (903 South 4th St., Hamilton, MT 59840; Tel: 406/363-9255, Fax: 406/363-9371). Their work, in collaboration with other colleagues, is reported in an article recently posted online in the Proceedings of National Science Foundation Early Edition.
GAS bacteria are common microbes that cause a variety of nasty diseases, including strep throat, wound infections, toxic shock, “flesh-eating” disease, scarlet fever, rheumatic fever, and kidney ailments. Musser and Beres seek to understand why some GAS strains cause severe infections while others lead to milder illnesses. By comparing the complete genomes of bacterial strains isolated from people with different GAS infections, the researchers hope to identify specific genes linked with individual diseases.
In their most recent study, the Rocky Mountain researchers determined the complete genetic sequence of an M3 GAS strain isolated from a person with toxic shock syndrome. M3 strains are known for causing extremely invasive infections leading to an unusually high degree of severe illness and death. The M3 strain genome contains more than 1.9 million base pairs. Approx. 1.7 million of those bases are shared with other, less deadly GAS strains, leaving approx. 10% of the genome unique to M3. When the researchers looked closely at the unique regions, they found genetic markers indicating that bacteriophages had brought in many of the additional M3 genes.
“What we have discovered is that bacterial viruses have imported crucial new toxin genes to create new virulence strains,” says Musser.
The M3 genome that the team sequenced has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxins A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A2, designated Sla.
Humans infected with the M3 strain had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA proved to be both pyrogenic and toxic for rabbits.
Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.
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