Source of Dangerous Heart Infection Discovered

Researchers have discovered important clues as to why a common bacterium can sometimes lead to a dangerous heart infection in children. Their findings were reported in the March 26, 2002, issue of the Proceedings of the National Academy of Sciences.

The bacterium, group A Streptococcus (GAS), causes acute rheumatic fever, the most common infectious cause of childhood heart disease in the world. In the United States, it has appeared in several localized outbreaks, and in 1999 the infection and its subsequent heart damage were responsible for 3,600 deaths. But GAS bacteria are relatively common and also cause a range of other diseases ranging from sore throats to toxic shock and flesh-eating disease. What makes different GAS strains invade different parts of the body, however, remains largely unknown. In addition, researchers have not known if different rheumatic fever outbreaks are caused by genetically similar bacteria or if different strains can emerge to cause the disease.

By isolating GAS bacteria from a person with the disease, scientists from the US National Institute of Allergy and Infectious Diseases (NIAID) have discovered several genes that are unique to those bacteria. Their discovery also reveals that two rheumatic fever outbreaks occurring 12 years apart in the area around Salt Lake City, Utah (USA), were caused by virtually identical GAS strains.

The study was directed by James Musser, Ph.D., chief of the laboratory of human bacterial pathogenesis at NIAID's Rocky Mountain Laboratories in Hamilton, MT (USA). Dr. Musser and colleagues determined the genetic blueprint of a GAS strain taken from a patient with rheumatic fever. All GAS bacteria that cause this disease are called M18 strains. The researchers then compared the M18 GAS blueprint to the DNA sequence of a non-M18 GAS strain, which does not cause the disease.

The researchers discovered several key differences between the two bacterial isolates. Although the M18 and non-M18 bacteria contained many of the same genes, the M18 strain had additional genes that appeared to encode novel bacterial toxins. In addition, most regions of variation between the two strains appeared to come from phages, viruses that can invade bacteria and insert large numbers of genes into the bacterium's own DNA. The presence of swappable toxin genes has important implications for understanding GAS outbreaks because it provides a mechanism for bacteria to exchange genes among themselves.

To see if individual GAS bacteria had different combinations of those genes, the researchers analyzed 36 strains isolated during different rheumatic fever outbreaks
from different parts of the country. Those strains showed little or no genetic variability. In particular, the study showed that GAS bacteria isolated from patients during a 1998-1999 Salt Lake City outbreak were nearly identical to those isolated from patients during the 1986-1987 epidemic in the same area. Therefore, the later outbreak appeared to be caused by a resurgence of the bacteria that caused the earlier cluster of illnesses, not by a new strain invading the area.

This research reveals some of the secrets of group A strep and is a major accomplishment in our quest to understand an important childhood disease,” said Anthony S. Fauci, M.D., NIAID director.




Related Links:
National Institute of Allergy and Infectious Diseases (NIAID)