Medicine

Italian Soil Yields a New Antibiotic That Can Fight Drug-Resistant Bacteria

The new discovery shows promise in helping to treat the millions of Americans infected each year with antibiotic-resistant superbugs.

Francesca Yorke/Getty Images

Many common bacterial infections remain easily treated by antibiotics. But doctors, researchers, and public health officials have raised concerns about the proliferation of antibiotics in the food supply and in medical settings, as well as the ability of bacteria to mutate in response to any treatment humans throw at them.

Most antibiotics in use today were discovered half a century ago, during the “Golden Age” of antibiotic discovery between the 1940s and 1970s. Many of those antibiotics were developed from microbes in soil. Scientists have been focused for many years on developing synthetic drugs in the lab, worried that all the useful antibiotics in soil have already been found.

But this is not the case. The “pipeline is far from dry,” said Richard Ebright, professor and laboratory director at the Waksman Institute of Microbiology at Rutgers University.

Ebright and his colleagues developed a new antibiotic from a soil sample taken in Italy. Their antibiotic, called pseudouridimycin, is potentially significant because it shows great promise in fighting many strains of drug-resistant bacteria.

Structure of bacterial RNA polymerase, showing the binding sites for the new antibiotic pseudouridimycin (PUM) and the current antibacterial drug rifampin (Rif). PUM has a lower resistance rate and a smaller resistance target than Rif — just 2 to 4 positions where alterations that result in PUM-resistance (blue) vs. 27 positions where alterations result in Rif-resistance (red) — due to functional constraints on alteration of the binding site for PUM in the RNA polymerase active center. | David Degen and Richard H. Ebright, Rutgers University

Ebright called their research process “a return to the classic approach” of antibiotic discovery. His lab used new, more sophisticated screenings to test microbes found in soil. And his team dug up a winner, which they describe in the journal Cell.

“It turns out to be not only possible, but relatively easy to find new classes of relatively potent antibacterial agents that were missed before,” Ebright said.

Pseudouridimycin (PUM) is unique in the way it fights bacteria. It blocks bacterial RNA polymerase, an enzyme used in the transcription of DNA to RNA. It does this, Ebright said, by mimicking a nucleoside-triphosphate, one of the “building blocks” of RNA that is essential for life. While bacteria often mutate by changing binding spots on the surface of the enzyme, PUM binds to a crucial part of the enzyme that nearly all bacteria need, enabling it to thwart even the most insidious of foes.

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The interaction between PUM and RNA polymerase, Ebright said, “makes it much harder for the bacterium to develop resistance.”

“This is very promising,” said Dr. William Hanage, associate professor of epidemiology at Harvard University.

“We need more weapons in our arsenal,” Hanage, who was not involved in the study, said, “and this looks like it could be a new weapon.”

PUM has already been shown to be successful against Methicillin-resistant Staphylococcus aureus, or MRSA, one of the main superbug threats in hospital settings. Hanage added there's a need for broad-spectrum antibiotics like PUM that can fight many different types of infections.

But, he cautioned, PUM won’t be a cure-all. “Evolution is cleverer than you are,” he said, “there’s different ways to evolve resistance.”

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