Scientists have discovered how bacteria fend off a wide range of antibiotics, and blocking that defense mechanism could give existing antibiotics more power to fight dangerous infections.
Researchers at New York University said on Thursday that bacteria produce certain nitric oxide-producing enzymes to resist antibiotics. Drugs that inhibit these enzymes can make antibiotics much more potent, making even deadly superbugs like Methicillin-resistant Staphylococcus aureus or MRSA succumb, they said.
“Developing new medications to fight antibiotic resistant bacteria like MRSA is a huge hurdle, associated with great cost and countless safety issues,” said Evgeny Nudler of NYU Langone Medical Center, whose study appears in the journal Science. “Here, we have a short cut, where we don’t have to invent new antibiotics. Instead, we can enhance the activity of well-established ones, making them more effective at lower doses,” he said in a statement.
Drug-resistant bacteria such as MRSA are a growing problem in hospitals worldwide, killing about 19,000 people a year in the United States. Nudler’s team found that many antibiotics kill bacteria through the production of harmful charged particles known as reactive oxygen species, otherwise called oxidative stress. “Antibiotics cause bacteria to produce a lot of reactive oxygen species. Those damage DNA, and bacteria cannot survive. They eventually die,” Nudler said in a telephone interview. “We found nitric oxide can protect bacteria against oxidative stress.”
He said bacteria produce nitric oxide to resist antibiotics. The defense mechanism appears to apply broadly to many different types of antibiotics, he said. Nudler said many companies are testing various nitric oxide-lowering compounds called nitric oxide synthase inhibitors for use as anti-inflammatory drugs. He thinks a compound in this class could be made to reduce the amount of nitric oxide bacteria can produce, reducing their ability to resist antibiotics. That would mean researchers would not need to discover new antibiotics.