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Crocodiles May Offer Solution To Deadly Antibiotic-resistant Infections

Deadly antibiotic-resistant fungal infections could be beaten after a breakthrough discovery in crocodiles.

YEPPOON, Australia — Researchers say crocodiles might hold the key to a breakthrough in medical research.

A team from Australia’s La Trobe University focused on the crocodiles’ defensins, small proteins that detect and announce an infection to the immune system. “The defensins are able to change their activity based on the pH environment.

Defensins are proteins in plants and animals that form an important part of our innate immune system to protect against infection by microbial pathogens such as bacteria, fungus and viruses.

They were first discovered in the 1980s and more recently have been attracting attention as potential therapeutics for the treatment infectious disease and cancer.

Although most research effort has focused on human and plant defensins, very little is known about defensins from other species that could harbor unique and useful functions.

“Some therapeutic treatments act on healthy cells by accident whereas this mechanism could help to reduce these off-target affects and focus on what’s harmful.”

Saltwater crocodile defensin CpoBD13 harbours an intriguing antimicrobial activity dependent on environmental pH which is key to the body recognizing which area or cells are infected.

Based on the pH level of the cell’s outer wall, CpoBD13 will recognize and attack fungal infections.

Their findings could be used to create targeted treatment for fungal infections in humans which are becoming increasingly frequent due to growing antibiotic resistance.

Scott Williams, a doctoral candidate from the University’s Institute for Molecular Science and lead author of the study, said: “Crocodiles have great antifungal defenses, and hopefully we’ll be able to adapt their defense to our own needs.

“We solved structures of crocodile defensins and they look surprisingly like the same proteins in humans, which means we could use them as a template to treat fungal infections in humans.”

Writing in the  Nature Communications journal, he said the reptiles use a unique pH sensing mechanism which has never been found before.

He added: “We haven’t seen the pH sensing mechanism in any other animal or plant.

“The defensins are able to change their activity based on the pH environment, so we could engineer other defensins to turn off or on depending on the presence of infection.

“Some therapeutic treatments act on healthy cells by accident whereas this mechanism could help to reduce these off-target affects and focus on what’s harmful.”

Senior author Professor Mark Hulett said that the study is also the first to document the structure of the defensin membrane attack in high resolution.

He added: “We were able to generate structural data to define how defensins attack and kill fungal pathogens.

“Consequently, our findings provide a model for understanding the anti-microbial activity of other defensins including those in humans.”

They used crocodiles from Koorana Crocodile Farm in Yeppoon, Queensland, the first commercial crocodile farm in Australia to conduct their unusual research.

Crocodile at Koorana crocodile farm Queensland, Australlia.  Commercial crocodiles were used to conduct the research. Shelly Collins /Unsplash.

 

Edited by Deborah .C. Amirize and Virginia Van Zandt

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