The best defense against a deadly superbug might be a virtual offense.
Duke University researchers are expanding upon a computer program they invented last year to predict how a rapidly mutating, infectious bacterium will evolve to evade the drugs used against it. Getting a glimpse into what the germ might do can allow scientists to develop a quicker drug counterattack.
"Now, there are cycles of alternating drug development, resistance, drug development, resistance," said Dr. Bruce Donald, co-author of the findings, which were published last week in the Proceedings of the National Academy of Sciences. "The algorithm opens the possibility that instead of retrospectively addressing it, you can observe resistance beforehand and then design the drug ahead of time."
Think of it as a game of chess, the researchers say. Advance knowledge of your opponents' moves can help you come up with pre-emptive strategies to beat them.
In this case, the opponent is methicillin-resistant Staphylococcus aureus - commonly called MRSA (pronounced MUR-sah). It's a growing problem in hospitals and other health care settings where open wounds, close quarters and vulnerable immune systems increase the risk of infection.
In recent years, the MRSA bug infiltrated the wider community as well. In 2007, North Carolina public health officials feared an outbreak when several cases were confirmed in counties including Guilford,Orange and Northampton.
"About five years ago, we began seeing a dramatic increase in the number of children in the emergency room or admitted to the hospital with significant infections," said Dr. Mark Piehl, medical director of WakeMed Children's Hospital.
Although most cases don't go beyond mild skin sores, the infection can become deadly if the bacteria tunnel deep into the body and invade blood, bones or key organs such as the heart and lungs.
According to the Centers for Disease Control and Prevention, about 19,000 Americans die from MRSA infection each year. The MRSA death rate in the United States is even higher than the AIDS death rate.
The germ is so dangerous because it can rapidly mutate, enabling it to develop resistance against antibiotics. A history of use and overuse of antibiotics in hospitals, ironically, is thought to have unwittingly fostered the microbe's strength, earning it a "superbug" reputation.
When novel mutations are discovered, new drugs must be designed from scratch to fight the changed version. Predicting the bacteria's transformations before they occur would let scientists make effective drugs earlier.
That's where Duke's computer program comes in.
To apply the program they created, called K* (pronounced K star), to MRSA, Donald and colleagues put themselves in the shoes of their tiny enemies. From the bug's point of view, a successful mutation accomplishes two things: It pushes off the antibiotic trying to kill it but still allows the organism to carry out the normal functions it needs to survive.
Virtual mutants ranked
The algorithm generates a vast assortment of possible mutants and then ranks them by which versions best accomplish both goals.
To test its accuracy, the researchers put on traditional white coats and gloves. At the University of Connecticut, colleagues of the Duke scientists artificially created the MRSA mutants in the laboratory.
They found that the real mutant bugs acted in ways that matched the virtual predictions. "There was a striking correspondence," Donald said.
The researchers expect the program's general design can eventually work for other bugs besides MRSA. Any microbe that evolves resistance by similar mutation methods is fair game, Donald said.
The authors are making their software freely available for any researcher who wants access.
"This work is very important," said Piehl, who was not involved with the algorithm's development. "Even the drugs that we are using may eventually become ineffective. We need to have access to other antibiotics against an ever-changing MRSA strain."
