AGH scientists clock bacteria's race to mutate

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Scientists at Allegheny General Hospital say they've documented that a particular strain of bacteria mutated much more quickly than previously thought over the course of an infection, perhaps explaining why some infections become chronic.

Reporting last week in the online journal PLoS Pathogens, researchers said their study showed that a group of related bacterial strains mutated so fast that the host immune's system couldn't keep up with the changes.

"As far as we know, this is the first report documenting definitively that bacteria during a single chronic or persistent infection undergo multiple mutations so that during the course of infection a group of related, but still different, strains are produced," said microbiologist Garth Ehrlich, scientific director of the Center for Genomic Sciences and the senior author of the paper. "The rate of change was much higher than we anticipated."

Jeffrey Weiser, professor of microbiology and pediatrics at the University of Pennsylvania and an editor at the journal, said the research confirms what other studies have shown in mice.

In this case, the subject was a child at Children's Hospital of Pittsburgh with chronic lung and ear infections and the specimens of Streptococcus pneumoniae -- a pathogen associated with meningitis and pneumonia -- were collected over seven months.

It's well known that viruses mutate to confuse the immune system. But Dr. Ehrlich said the study suggests that bacteria, which cause most chronic infections, seem to be doing the same thing, and very quickly.

The practical impact of the study won't be immediate, but the researchers said a better understanding of the mutation process will aid in eventually developing treatments.

Bacterial infections were once thought to be caused by a single organism, but the AGH team and other researchers have shown that some infections are the result of multiple strains of bacteria living together in what are called biofilms.

In those communities, bacteria appear to incorporate DNA from neighboring bacteria into their own genomes in a process called horizontal gene transfer, which has been studied since the 1970s.

The AGH study examined the rate of that gene transfer among strains of Streptococcus pneumoniae. In comparing the original strain that started the infection with strains examined at the end of the seven months, the study says, 7.8 percent of the genome had changed.

That pace outstrips the ability of the immune system, which also realigns the genomes of white blood cells so they can recognize and attack invaders.

In this genomic "chess match," Dr. Ehrlich said, the bacteria stays "one step ahead" and the infection persists.

The AGH team said its next step is to do a broader study of gene transfer involving more species of bacteria.

"We suspect that this is not the only species of bacteria that does this," said Dr. Ehrlich.


Torsten Ove: tove@post-gazette.com or 412-263-1510.


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