Down with the (antibiotic) resistance!

How do you stop a superbug from fighting an antibiotic? Try giving it another enemy.

Acinetobacter baumannii is a bacterium fairly commonly found in hospitals that can cause infections in the lungs, blood and urinary tract. This fast-mutating bug easily overcomes antibiotics, so it’s difficult to manage.

Now, a team from Australia’s Monash University, led by Fernando Gordilla Altamirano, has found a way to reverse antibiotic resistance in A. baumannii by using phages to trick the bacteria into letting down their guard.

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Key research points

• Antibiotic resistance can be reversed using phages
• Phages use bacterium A. baumannii’s protective layer as an entry target
• A. baumannii mutates to defend against phage attack
• Mutations lead to loss of protective layer and allow antibiotic entry

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Phages are viruses that target bacteria specifically by injecting viral components into the bacterium to kill it. They’re well-established as useful tools for overcoming antibiotic resistance, but it hasn’t always been clear exactly why.

In a paper published in Nature Microbiology, the authors describe the mechanism by which phages achieve this. The phages attack A. baumannii, forcing it to mutate out of defence, thereby changing its protective layer enough to reverse resistance to the antibiotics.

“A. baumannii produces a capsule, a viscous and sticky outer layer that protects it and stops the entry of antibiotics,” says Gordillo Altamirano.

The phages target the capsule layer by using it as their entry point. This forces the bacterium to stop making the layer, leaving it naked and exposed to antibiotics.

“In an effort to escape from the phages, A. baumannii stops producing its capsule, and that’s when we can hit it with the antibiotics it used to resist,” says Gordillo Altamirano.

This takes advantage of the fast-mutating nature of bacteria and turns A. baumannii’s strength into a weakness.

“We have a large panel of phages that are able to kill antibiotic-resistant A. baumannii,” says co-author Jeremy Barr. “But this superbug is smart, and in the same way it becomes resistant to antibiotics, it also quickly becomes resistant to our phages.”

The study focused on two specific phages called ΦFG02 and ΦCO01, which were able to help resensitise at least seven different antibiotics. They used mice models for the research, which provides exciting potential for the future.

“The phages had excellent effects in experiments using mice, so we’re excited to keep working on this approach,” says Gordillo Altamirano.

“We’re showing that phages and antibiotics can work great as a team.”

After all, the enemy of my enemy is my friend.

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Spotlight: Antimicrobial resistance

• Antimicrobial resistance (AMR) is a big health concern
• It occurs when germs mutate to resist medicines and antibiotics
• This can lead to infections which extend hospital stays
• Only use antibiotics at the direction of your health care provider

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