A breakthrough discovery: Sugar Cane emerges as a game-changer in the fight against antibiotic resistance.

It is very efficient against pathogenic bacteria, including those resistant to commonly used antibiotics like fluoroquinolones, and has an extraordinarily high efficacy at tiny doses.

A powerful plant toxin with a novel method of killing dangerous bacteria has emerged as one of the most promising new antibiotic candidate in decades.

The sugar cane leaf scald disease-causing bacterial plant pathogen Xanthomonas albilineans produces albicidin, an antibiotic.

Albicidin, a natural compound found in plants, proves to be a powerful weapon against antibiotic-resistant superbugs. 

Originally used by pathogens to infect plants, scientists have discovered its effectiveness in destroying harmful bacteria such as E. coli and S. aureus. 

The growing threat of antibiotic resistance has made the development of new drugs crucial, and albicidin’s potential as an antibiotic candidate is highly promising.

Albicidin’s potential as an antibiotic has been hindered by scientists’ lack of understanding of how it interacts with its target, the bacterial enzyme DNA gyrase. 

Albicidin has shown low toxicity in pre-clinical experiments and has antibiotic properties, but its development as a pharmaceutical drug has been stalled. 

DNA gyrase plays a crucial role in the cell by binding to DNA and supercoiling it, a process necessary for proper cellular function.

Now, using advances in cryo-electron microscopy, the lab of Dr. Dmitry Ghilarov at the John Innes Centre, along with those of Professor Roderich Süssmuth at Technische Universität Berlin, Germany, and Professor Jonathan Heddle at Jagiellonian University, Poland, have captured the first image of albicidin bound to gyrase.

Scientists discovered that albicidin forms an L-shape, allowing it to interact with both DNA gyrase and DNA in a novel manner. This interaction prevents gyrase from moving and twisting the DNA, effectively blocking its function. 

The action of albicidin is similar to throwing a wrench into a machinery, disrupting its normal function. 

This unique mode of interaction with gyrase is distinct from existing antibiotics, increasing the likelihood that albicidin and its derivatives will be effective against antibiotic-resistant bacteria.

“It seems by the nature of the interaction, albicidin targets a really essential part of the enzyme and it’s hard for bacteria to evolve resistance to that,” explains Dr. Ghilarov. “Now that we have a structural understanding, we can look to further exploit this binding pocket and make more modifications to albicidin to improve its efficacy and pharmacological properties.”

Building on this discovery, the research team has begun to chemically synthesize variations of albicidin with enhanced properties. In laboratory tests, these modified versions have shown efficacy against some of the most hazardous hospital-acquired bacterial infections, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium.

Dr. Ghilarov believes “this is one of the most exciting new antibiotic candidates in many years. It has extremely high effectiveness in small concentrations and is highly potent against pathogenic bacteria – even those resistant to the widely used antibiotics such as fluoroquinolones.” 

“This molecule has been around for decades,” adds Dr. Ghilarov, “Now advances in cryo-electron microscopy has made it possible to determine structures of even the most elaborate protein-DNA complexes. To be the first person to see the molecule bound to its target and how it works is a huge privilege, and the best reward one can have as a scientist. But this work is a big team effort, and we would not have done it without our European colleagues.” 

Moving forward, the research team aims to collaborate with academic and industry partners and secure funding to advance the research to human clinical trials. 

This progress could result in the creation of a new class of antibiotics, desperately needed to combat the growing global threat of antimicrobial resistance (AMR).

Source: Nature

Image Credit: Getty

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