Subtle changes mark common drug-resistant bacteria

HOUSTON -- (November 19, 2007) -- Subtle differences in the genetic content of a form of methicillin-resistant Staphylococcus aureus or MSRA may account for the bacterium's ability to cause serious infections in otherwise healthy individuals, said Baylor College of Medicine and Texas Children's Hospital researchers who sequenced the organism's genome.

In a report that appeared online in the open-access journal BMC Microbiology, Dr. Sarah Highlander, associate professor of molecular virology and microbiology at BCM, and her colleagues described the subtle changes that distinguish the USA300 form of MRSA from others around the country.

"The strain we sequenced in Houston is significant as the most common strain causing skin infections as well as serious invasive infections in the United States," said Highlander. "These strains were not found or only rarely found causing community infections prior to 2000. Now they account for over 70 percent of the S. aureus (staph aureus) isolates recovered from children at Texas Children's with community acquired infections.

The research began with Dr. Sheldon Kaplan, professor of pediatrics at BCM, who became concerned after noting the rapid increase in these MRSA isolates in patients at Texas Children's, especially when a teen-age football player died precipitously of the infection after sustaining a knee injury.

Kaplan contacted Dr. George Weinstock, co-director of the BCM Human Genome Sequencing Center, to find out if it would be possible to determine the genetic sequence of the bacterium. Weinstock has pioneered bacterial sequencing and is a driving force behind the National Institutes of Health Human Microbiome Project.

"The question is why is this one dominant?" said Weinstock, senior author of the report. This form of MRSA is the most common type in the United States and by far the most predominant in Houston.

Whereas other flourishing strains of bacteria often have many changes in their genetic structure, the changes in this one are subtle, said Weinstock and Highlander.

"Somehow, those subtle differences, possibly in only a few key genes, make all the difference," Weinstock said. "With this new genome sequence we are now in a position to zoom in on these critical functions."

The bacteria has also picked up an accessory chromosome called a plasmid that carries genes conferring resistance to many important antibiotics, including bacitracin, a common component of antibiotic skin ointments sold over the counter, said Highlander. The bacterium has also picked up a chunk of genetic material found in Staphylococcus epidermidis, a benign form of the bacterium living on the skin. In fact, this chunk of genes oversees production of arginine deiminase, which may help the bacterium to survive on the skin.

"Another major question is why some people become seriously ill from this strain and others do not," said Highlander.

Answering the question has important public implications. Thirty years ago, methicillin resistant forms of the staph bacteria accounted for 2 percent of infections. By 2003, they accounted for 64 percent of such infections.

The article is available at http://www.biomedcentral.com/content/pdf/1471-2180-7-99.pdf. A full list of authors is available there.

Funding for this project came from the Vivian L. Smith Foundation, Prisma Energy International and Texas Children's Hospital and Baylor College of Medicine in Houston.