New mechanism controls superbugs by sparing the death sentence

New mechanism controls superbu...
A colony of Pseudomonas aeruginosa grown in a dish for three days
A colony of Pseudomonas aeruginosa grown in a dish for three days
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A colony of Pseudomonas aeruginosa grown in a dish for three days
A colony of Pseudomonas aeruginosa grown in a dish for three days

Antibiotics are reaching the limits of their usefulness, as they drive bacteria to evolve into new drug-resistant forms. But a new study has uncovered a mechanism that could make the bugs non-infectious without killing them, reducing the evolutionary pressure that leads to superbugs.

Humans are currently locked in an arms race with bacteria. Antibiotics were an incredibly important scientific development, but over the decades bacteria found ways to survive them. So we came up with better drugs – and the bacteria came up with better defenses.

Unfortunately, it’s beginning to look like we’re losing this battle. Our antibiotic arsenal is drying up, and some bacteria are now resistant to everything we can throw at them. New drugs are always in the works, but development is slow-going and only delays the inevitable. Ideally, we need a solution that doesn’t contribute to further resistance, lest we face a future where unchecked superbugs are killing up to 10 million people a year.

And that was the goal for the new study. Researchers at the University of Geneva (UNIGE) have identified a protein that, when switched off, seems to render bacteria harmless. Importantly, it doesn’t stop them multiplying, meaning there’s no evolutionary motive for them to rapidly evolve resistance.

The team was investigating a type of protein called an RNA helicase that they suspected played a role in the virulence of bacteria. Pseudomonas aeruginosa was the target – a nasty, opportunistic bacteria that’s becoming harder and harder to treat due to drug resistance.

The researchers engineered P. aeruginosa to be unable to express this RNA helicase, and observed how it handled things both in a lab culture and in an animal model. In the latter case, that model was a Galleria mellonella larvae, which is often used to study interactions between hosts and pathogens due to its immune system’s similarities with mammals.

The team found that the bacteria living in a dish could still multiply just fine without the RNA helicase, but the insect tests suggested that it had a diminished ability to infect living cells. The team infected a group of the larvae with the bacteria that couldn’t produce RNA helicase, and found that more than 90 percent of the larvae survived the experiment. That’s far greater than the 20 percent that survived infection by the unedited P. aeruginosa strain, and closer to the 100 percent that survived in the control group that weren’t exposed to any bacteria.

The team says that this gentler method of controlling pathogens could open a new path for treating infections that may put an end to the arms race.

“From an antimicrobial drug strategy point of view, switching off the pathogen’s virulence factors rather than trying to eliminate the pathogen completely, means allowing the host immune system to naturally neutralize the bacterium and potentially reduces the risk for the development of resistance,” says Martina Valentini, corresponding author of the study. “Indeed, if we try to kill the bacteria at all costs, the bacteria will adapt to survive, which favors the appearance of resistant strains.”

The next steps for the team are to screen a library of known drug molecules for any that may block RNA helicase proteins, to induce the desired effect. Other recent studies are making progress in this kind of control: one used vaccines to steer the path of bacterial evolution into harmless dead ends, while another trained up viruses that prey on bacteria to anticipate their most likely mutations and cut them off.

The research was published in the journal Nucleic Acids Research.

Source: UNIGE

1 comment
1 comment
Sounds like a game changer to me with our penchant for demanding antibiotics from our doctors for the slightest sniffle which has put us in this bad position in the first place.