The discovery of plant toxins could advance the fight against antibiotic resistance
A powerful plant toxin with a unique way of killing harmful bacteria has emerged as one of the most powerful antibiotic candidates in decades.
Scientists say that albicidin can kill superbugs such as E.coli and salmonella, which are becoming increasingly resistant to modern medicine.
It is produced by a sugarcane pathogen called Xanthomonas albilineans, which causes the devastating disease leaf smut in plants.
It is believed that albicidin is used by the pathogen to attack sugar cane, allowing it to spread.
Scientists have known for some time that albicidin is very effective at killing superbugs like E.coli, which are notorious for becoming increasingly resistant to antibiotics.
This means that researchers are racing to develop new effective drugs.
While experiments have shown that albicidin shows promise, so far pharmaceutical development has been hampered because scientists did not know exactly how it interacts with its target, DNA of a bacterial enzyme called gyrase.
This enzyme binds to DNA and bends it through a series of elegant movements in a process called supercoiling, which is vital for cells to function properly.
Now researchers in the UK, Germany and Poland have exploited advances in a technique called transmission electron microscopy, which allows samples to be examined at temperatures as low as 273°C.
They found that albicidin forms an L-shape, which allows it to interact with both gyrase and DNA in a unique way.
In this state, gyrase can no longer move to bring the ends of the DNA together, and albicidin acts like a wrench thrown between two gears.
The researchers say that the way albicidin interacts with gyrase is different enough from existing antibiotics that the molecule and its derivatives are likely to work on many of the current antibiotic-resistant bacteria.
Study author Dr Dmitry Ghilarov of the John Innes Center in Norwich said: “It seems that because of the nature of the interaction, albicidin targets a really essential part of the enzyme and it is difficult for bacteria to develop resistance to it. .
“Now that we have a structural understanding, we can try to further exploit this binding pocket and make further modifications to albicidin to improve its potency and pharmacological properties.”
The team has already used their observations to make improved versions of the antibiotic.
Tests showed that these new versions were 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 has extremely high potency at low concentrations and is very effective against pathogenic bacteria – even those resistant to commonly used antibiotics such as fluoroquinolones.
“This molecule has been around for decades. Now, advances in cryo-electron microscopy have made it possible to determine structures of even the most complicated protein-DNA complexes.
“Being the first person to see how the molecule is bound to its target and how it works is a great privilege and the best reward a scientist can have.”
– The results are published in the journal Nature Catalysis.