The discovery of plant toxins could accelerate the fight against antibiotic resistance

A powerful plant toxin with a unique way of killing harmful bacteria has become one of the strongest antibiotic candidates in decades.

Scientists say albicidin can kill superbugs like E. coli and salmonella, which are becoming increasingly resistant to modern medicine.

It is produced by a sugar cane pathogen called Xanthomonas albilineans, which causes a devastating leaf disease in plants.

Albicidin is believed to be used by the pathogen to attack sugar cane, allowing it to spread.

Scientists have known for some time that albicidin is very effective in killing superbugs such as E. coli, which are notorious for becoming increasingly resistant to antibiotics.

This means that scientists are racing to develop effective new drugs.

While experiments have shown albicidin to be promising, its pharmaceutical development has so far been hampered because scientists didn’t know exactly how it interacts with its target, a bacterial DNA enzyme called gyrase.

This enzyme binds to the DNA and twists it through a series of elegant movements in a process called supercoiling, which is essential for proper cell function.

Now, scientists from the UK, Germany and Poland have taken advantage of advances in a technique called transmission electron microscopy, which allows samples to be examined at temperatures as low as minus 273°C.

They found that albicidin forms an L-shape, allowing it to interact with both gyrase and DNA in a unique way.

In this state, gyrase can no longer move to join the ends of the DNA, and albicidin acts as a key thrown between two gears.

The researchers say the way albicidin interacts with gyrase is sufficiently different from existing antibiotics that the molecule and its derivatives are likely to work against many current antibiotic-resistant bacteria.

Study author Dr Dmitry Ghilarov, from the John Innes Center in Norwich, said: ‘It seems that due to the nature of the interaction, albicidin attacks a really important part of the enzyme and it is difficult for bacteria to develop resistance to it.

“Now that we have a structural understanding, we can further exploit this binding pocket and make more modifications to albicidin to improve its efficacy and pharmacological properties.”

The team has already used their observations to create improved versions of the antibiotic.

Tests have shown that these new versions are effective against dangerous infections such as E. coli and salmonella.

Dr Ghilarov said: “We believe this is one of the most exciting new antibiotic candidates in many years.

“It is extremely effective at low concentrations and very potent against pathogenic bacteria – even those that are resistant to commonly used antibiotics such as fluoroquinolones.

“This molecule has been around for decades. Currently, advances in cryo-electron microscopy have made it possible to determine the structures of even the most complex protein-DNA complexes.

“Being the first person to see a molecule related to a target and how it works is a huge privilege and the best reward you can get as a scientist.”

– The results have been published in the journal Nature Catalysis.

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