Bacteriophages Create Deadly New Strep Strains

The discovery, reported in the July 16, 2002, online edition of Proceedings of the National Academy of Sciences (www.pnas.org), highlights an important mechanism for bacterial evolution and identifies several potential targets for vaccines or drugs to prevent or treat some severe infections.

Group A Streptococcus (GAS) bacteria are common microbes that cause many different diseases, including strep throat, wound infections, toxic shock, "flesh-eating” disease, scarlet fever, rheumatic fever, and kidney ailments. To understand why some GAS strains cause severe infections while others lead to milder illnesses, James Musser, M.D., Ph.D., of the US National Institute of Allergy and Infectious Diseases (NIAID; www.niaid.nih.gov), and colleagues turned to the GAS genome. By comparing the complete genetic blueprints of bacterial strains isolated from people with different GAS infections, they are hoping to identify specific genes linked with individual diseases.

In their most recent study, Dr. Musser and colleagues determined the complete genetic blueprints of a so-called M3 GAS strain isolated from a person with toxic shock syndrome. This strain contains more than 1.9 million base pairs. Around 1.7 million of those are shared with other, less deadly GAS strains, leaving about 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 M3 genes. "What we have discovered is that bacterial viruses have imported crucial new toxin genes to create new virulence strains,” says Dr. Musser, who directs the human bacterial pathogenesis laboratory at NIAID's Rocky Mountain Laboratories in Hamilton, MT (USA).

Among the unique genes, the researchers identified several that encode bacterial toxins and enzymes that may contribute to the highly infective nature of M3 GAS bacteria. One of the toxins resembles an enzyme found in snake venom. These molecules may prove to be useful targets for new drugs, diagnostics, or vaccines.

"Scientists have known about bacteriophages for a long time,” explains Dr. Musser, "but they have not been extensively studied for their indirect contributions to infectious diseases. Now that we have shown their importance to bacterial evolution, there is much we need to know about them.” Researchers from the University of Minnesota Medical School and The US National Jewish Medical and Research Center in Denver also contributed to this study.