Crocodiles rock: Filthy crocs’ immune systems may hold the key for treating fungal infections in humans

Researchers at Melbourne’s La Trobe University have found out why crocodiles have a high tolerance to fatal fungal infections and they think it might lead to different treatemnts in humans.

“Crocodiles live in such microbial-rich environments and yet they rarely get infections,” La Trobe PhD candidate and leading researcher in the study Scott Williams tells Cosmos.

“Even though they’re in territorial disputes, they lose limbs, they’re rarely contracted,” Williams says. “It led us to believe there’s something about the immune system which is making them resilient. And we wanted to research this further and find out if there was something that we could use, translating that to human health, potentially finding the basis for future therapeutics.”

Williams adds that “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.”

The team focused on crocodile defensins – proteins that bind to pathogens to announce an infection to the immune system.

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Looking at the crocodile genome, the researchers were able to find homologues of human defensins in the genetic code. By taking the DNA sequence and placing it into yeast, they were able to purify the proteins.

“We were then able to treat the pathogens that we have at hand here at La Trobe, and that’s when we noticed that it was particularly potent,” says Williams.

“We tested against Candida albicans, which is one of the biggest threats at the moment. The World Health Organization just released a list of the emerging fungal pathogens that we should be researching, and this was number one. We know can cause thrush, but it can actually kill people.”

Williams says the research is particularly important as antibiotic resistance builds up in fungi.and because fungal infections are adapting to the warming climate, which is making them more of a threat.

The team also found that the crocodile defensin CpoBD13 possesses a never-before-seen response to pH levels.

At neutral pH, 7, the defensin was inactive. “When the pH was lowered, slightly acidic, it was turned on and able to clear the fungal cells,” Williams explains.

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Using the Australian Synchrotron, Williams’s co-supervisors, Professors Marc Kvansakul and Mark Hulett, were able to resolve the structure of the protein and found that the defensins relied on residues being present on the fungal cell walls, lowering the pH allowing them to kill the fungal infection.

Williams’s team believe their findings could allow engineering of defensins with pH-dependent activity in biotechnology and therapeutic applications, like treating serious infections in humans or crop defence.

The results are published in Nature Communications.

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