NU researchers say genetic approach might prevent bacteria from resisting drugs

For hospital patients with weakened immune systems, a growing worry is a potentially deadly infection by drug-resistant bacteria such as MRSA or tuberculosis.

But by examining bacteria’s own primitive immune systems, two Northwestern University researchers may have found a way to prevent or slow the development of drug resistance.

If applied clinically, the method could prolong the effectiveness of antibiotics at a time when doctors worry that many are losing their power to fight bacterial infections.

Like students passing around the answers to a test, bacteria can share the genes necessary for drug resistance through a process called horizontal gene transfer—rendering infections untreatable by common antibiotics such as penicillin and methicillin.

But on Friday in the journal Science, microbiologists Luciano Marraffini and Erik Sontheimer describe a gene sequence, called CRISPR, that protects bacteria against the transmission of harmful genes by attacking invading DNA.

The scientists suggest that this natural defense system could be modified to trick bacteria into thinking antibiotic resistance was an unwelcome visitor to fight off, rather than a gift to embrace.

Sontheimer cautions that any clinical application remains in the distant future. He also does not know whether it would be possible to fight an acute infection in this way, returning resistant bacteria to a vulnerable state.

Still, he said, the system shows promise as a means of treating dangerous bacteria strains to prevent them from developing new resistance.

“We’ll never have the killer drug that just ends bacterial infections; it will be an ongoing arms race,” Sontheimer said. “But if we can extend the useful life of antibiotics that are already out there, that will be one more arrow in our quiver in this fight against infectious disease.”

Methicillin-resistant Staphylococcus aureus, or MRSA, causes serious infections in almost 100,000 people and kills nearly 20,000 each year in the U.S., according to the Centers for Disease Control and Prevention. There is also concern over drug-resistant strains of other diseases, such as tuberculosis and Clostridium difficile, or C. diff.

With little promise of new antibiotics from pharmaceutical companies, many infectious-disease doctors are worried about a continued resurgence of bacterial disease unless strategies like Marraffini and Sontheimer’s bear fruit.

“The news is bad, which is why alternate strategies like this that attempt to target or limit the emergence of resistance are exciting,” said Dr. Neil Fishman, director of the Antimicrobial Management Program at the University of Pennsylvania. “If it would prevent the emergence of further resistance or the spread of resistance, that would be helpful.”

Perhaps a drug could be administered with a new antibiotic to prolong its usefulness, doctors said, or given to patients not yet colonized by resistant bacteria.

“It’d be like a second line of defense,” said Laurie Tompkins, chief of the genetic mechanisms branch at the National Institute of General Medical Sciences, “and we need all the lines of defense we can get.”

rmitchum@tribune.com