A new antibiotic uses sneaky tactics to kill drug-resistant superbugs

Drug-resistant bacteria have a new challenger.

A new molecule can kill deadly strains of common bacteria, such as Escherichia coli and Klebsiella pneumonia, that are resistant to most existing antibiotics. The drug works differently from currently available antibiotics, potentially making it harder for bacteria to develop resistance, researchers report September 12 in Nature.

Most antibiotics kill bacteria by weakening their cell wall or by preventing the production of certain proteins. But bacteria have, over time, evolved ways to circumvent these drugs. And as antibiotics are used frequently in both hospitals and agriculture, resistant bacterial strains are becoming more common. Infections with multidrug-resistant microbes are particularly worrisome, because they can turn usually easy-to-treat illnesses like strep throat or urinary tract infections into deadly ordeals. 

The newly developed drug uses a different tactic. It inhibits a key enzyme in the cell membrane that helps the bacteria secrete proteins. “We’re hitting a new target,” says study coauthor Peter Smith, an infectious disease researcher at Genentech, a biotech company based in South San Francisco, Calif. That means that strategies that bacteria use to evade existing antibiotics won’t work here, giving the molecule an edge.

When the enzyme is blocked, proteins build up in the cell membrane until the membrane bursts, ultimately killing the cell, says Floyd Romesberg, a chemist at the Scripps Research Institute in La Jolla, Calif., who wasn’t part of the study. Romesberg developed precursors to the antibiotic in his lab, but the new version is more effective, he says.

In tests in cultured cells and mice, the molecule killed off a variety of common gram-negative bacteria that cause infections in humans, including E. coli and Pseudomonas aeruginosa, and was also effective against gram-positive bacteria. Gram-negative bacteria, so called because of how they appear when stained for viewing under a microscope, are notoriously difficult to attack with antibiotics because of the microbes’ hard-to-penetrate cell membrane (SN: 6/10/17, p. 8). The drug also destroyed bacterial strains that are resistant to multiple kinds of antibiotics.  

The molecule will need to go through additional testing and tweaking before it can be used in humans, Smith says. And it’s not a permanent solution to the growing problem of antibiotic resistance. Eventually, if molecules of this type are widely used as antibiotics, bacteria will evolve resistance, as they always do. But for now, it’s a step ahead.