How crocodiles resist deadly fungal infections

Amazing stuff!

"... Saltwater crocodiles use a pH sensing mechanism to attack and kill fungal pathogens ...
For the first time, scientists have discovered a unique component of a saltwater crocodile’s physiology that helps its immune system identify and kill fungal infections. It's this that allows them to thrive in microbe- and pathogen-laden waters infection-free, despite frequently sporting wounds from territorial disputes in the wild. ...
Researchers ... have isolated a unique pH-sensing mechanism made up of small proteins, known as defensins, that detect infection and alert the immune system. The alarm-sounding role of the defensins is so far unique to these reptiles and hasn’t been identified in any other plant or animal. ...

Discovered in the 1980s, defensins are an integral part of the immune systems of plants and animals, and help protect against microbial pathogens such as bacteria and fungus. Research has largely focused on human defensins, but little is known about the roles of the proteins in many other species.

In saltwater crocodiles, defensin CpoBD13 possesses antimicrobial activity that registers environmental pH levels. It enables the animal’s immune system to recognize which area or cells are infected and then attack and kill the fungal pathogen. ..."

"... the study is also the first to document the structure of the defensin membrane attack in high resolution. ..."

From the abstract:

"Crocodilians are an order of ancient reptiles that thrive in pathogen-rich environments. The ability to inhabit these harsh environments is indicative of a resilient innate immune system. Defensins, a family of cysteine-rich cationic host defence peptides, are a major component of the innate immune systems of all plant and animal species, however crocodilian defensins are poorly characterised. We now show that the saltwater crocodile defensin CpoBD13 harbors potent antifungal activity that is mediated by a pH-dependent membrane-targeting action. CpoBD13 binds the phospholipid phosphatidic acid (PA) to form a large helical oligomeric complex, with specific histidine residues mediating PA binding. The utilisation of histidine residues for PA engagement allows CpoBD13 to exhibit differential activity at a range of environmental pH values, where CpoBD13 is optimally active in an acidic environment."

Crocodile’s secret weapon against deadly infections could help save us They’ve been on the planet for around 83 million years, and their giant ancestor Deinosuchus is believed to have even dined on dinosaurs. But while the crocodile is best known as an aggressive apex predator, the reptile has plenty of attack power in its immune system too.

Crocodiles could save us from deadly infections A new study by La Trobe University researchers reveals how crocodiles resist fatal fungal infections using a unique pH sensing mechanism despite living in filthy water.

Crocodile defensin (CpoBD13) antifungal activity via pH-dependent phospholipid targeting and membrane disruption (open access)

Fig. 3: Crystal structure of the CpoBD13:PA complex