Applying crocodile’s unique pH sensing mechanism to benefit humans

Researchers from La Trobe University have just discovered how crocodiles, despite living in dirty water, prevent deadly fungal infections by employing a unique pH sensing mechanism.

The study, which was published in Nature Communications, could be applied to develop targeted treatments for human fungal infections, which are becoming more common as a result of rising antibiotic resistance.

Scott Williams, the study’s lead author from La Trobe University, concentrated on the defensins of crocodiles, which are small proteins that identify and alert the immune system to an infection.

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. Crocodiles have great antifungal defenses and hopefully we will be able to adapt their defense to our own needs.”

Scott Williams, Study Lead Author and Graduate Researcher, Biochemistry, La Trobe University

According to Scott Williams, no other plant or animal has ever had this function.

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.”

The study is also the first to capture in high detail the structure of the defensin membrane attack, according to senior author Professor Mark Hulett.

Using the power of the Australian Synchrotron, together with co-author Prof Marc Kvansakul, we were able 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 human.”

Mark Hulett, Study Senior Author and Head of Department, Biochemistry and Chemistry, La Trobe University

The crocodile tissue for this study was obtained by Professor Hulett from the Koorana Crocodile Farm in Yeppoon, Queensland, the country’s first commercial crocodile farm, with the assistance of John Lever and John McGrath.

Future therapeutics that could targeting infections

The study’s results could enable the development of defensins with pH-dependent activity for biotechnological and therapeutic applications, including the treatment of life-threatening human infections.

The saltwater crocodile defensin CpoBD13 possesses an unusual antibacterial property that is pH-dependent and essential for the body to identify which cells or areas are sick.

CpoBD13 will identify and combat fungal infections based on the pH of the cell’s outer wall.

What are defensins?

Defensins are proteins found in plants and animals that play a significant role in the human innate immune system’s defense against microbial pathogens such as viruses, bacteria, and fungi.

They were initially identified in the 1980s and have since gained popularity as prospective therapies for the treatment of cancer and infectious diseases.

Although the majority of study has concentrated on human and plant defensins, relatively little is known about defensins from other species that could harbor distinct and valuable activities.

La Trobe University’s Hulett Lab is spearheading research to better understand the function of plant and animal defensins to develop innovative therapies for treating human disease.