Medical

New drug target makes superbugs choke on their own toxic molecules

New drug target makes superbug...
Researchers have uncovered a new mechanism for killing antibiotic-resistant gram-negative bacteria such as E. coli
Researchers have uncovered a new mechanism for killing antibiotic-resistant gram-negative bacteria such as E. coli
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Researchers have uncovered a new mechanism for killing antibiotic-resistant gram-negative bacteria such as E. coli
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Researchers have uncovered a new mechanism for killing antibiotic-resistant gram-negative bacteria such as E. coli
An illustration of cardiolipin (red) at work in a bacterial cell, helping the transport machinery move lipopolysaccharide (blue) to the outer membrane
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An illustration of cardiolipin (red) at work in a bacterial cell, helping the transport machinery move lipopolysaccharide (blue) to the outer membrane
From left: Martin Douglass, Alexandria Purcell and Professor Stephen Trent, in a University of Georgia lab in 2019
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From left: Martin Douglass, Alexandria Purcell and Professor Stephen Trent, in a University of Georgia lab in 2019
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Antibiotic-resistant bacteria, or “superbugs,” pose one of the most dangerous looming threats to public health. Now, researchers at the University of Georgia have found a new potential weakness in some of the worst strains, which could make them choke on their own toxic molecules.

Antibiotics were one of the most important scientific discoveries of the 20th century, but decades of overprescription and misuse have drastically undermined their effectiveness. Pathogenic bacteria have rapidly evolved resistances to our drugs, and we’re very quickly running out of them. Scientists have warned that if we stay on our current path, superbugs could be responsible for 10 million deaths per year by 2050.

New antibiotics are sorely needed, and to give us the best chance they should work on a variety of mechanisms. And now, researchers have identified a new mechanism that future drugs could target to take out superbugs.

The study focused on gram-negative bacteria, a class of microbes that are particularly concerning. These bacteria have two cell membranes, which makes it much harder for antibiotics to get in. Plus, they produce toxic molecules called lipopolysaccharides (LPS), which can, among other things, trigger potentially life-threatening conditions like septic shock.

An illustration of cardiolipin (red) at work in a bacterial cell, helping the transport machinery move lipopolysaccharide (blue) to the outer membrane
An illustration of cardiolipin (red) at work in a bacterial cell, helping the transport machinery move lipopolysaccharide (blue) to the outer membrane

The key to the new study was a molecule called cardiolipin. What exactly this molecule did within bacteria had long been a mystery, so to find out the researchers engineered E. coli to make it unable to produce cardiolipin. And, intriguingly, it turns out that this one molecule plays a vital role in both of the gram-negative defense mechanisms.

The team found that, without cardiolipin, the E. coli could no longer transport the toxic LPS from its center to the cell surface. Instead, these toxic molecules build up inside until it bursts open, killing the bacterium. Those that do survive will have weakened outer membranes, meaning existing antibiotics will have an easier time finishing them off.

“This paper is one of the first to link cardiolipin to maintaining the outer membrane of E. coli,” says Martin Douglass, lead author of the study. “Future therapeutics could target aspects of this process and make gram-negative bacteria vulnerable to antibiotics.”

The research was published in the journal PNAS.

Source: University of Georgia

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Ralf Biernacki
Antibiotics are being fed to livestock---chickens, pigs, cattle---by tonnes, enough so that soils fertilized with their manure have their soil bacteria decimated. Meat on supermarket shelves, coming from these animals, is also testing positive for antibiotics. These antibiotics are not used to cure livestock that is ill---ill livestock is culled, not cured. The antibiotics are fed to healthy livestock, en masse, because they accelerate the fattening process, and thus increase profits. This has been going on for decades, completely ignored by "watchdog" regulatory agencies. Gee, I wonder where all these antibiotic-resistant bacteria are coming from. From hospitals, surely?