CRISPR Contrives Secret Lives Of Antimicrobial Peptides

CRISPR-Cas9 gene editing technology was used to systematically delete AMP genes, going as far to delete all the known AMPs in fruit fly animal models, in a manner that was intended to have a clarifying effect.

AMPs are mysterious, and not fully understood despite their importance to innate immunity. AMPs have been shown to kill fungi and bacteria in some in vitro studies, however behavior of AMPs in living organisms is not as easily examined, as there are too many factors involved in innate immunity making isolating effects of individual AMPs in a living organism is a very complex proposition.

Using CRISPR-Cas9 technology Ecole Polytechnique Federal de Lausanne scientists deleted 14 AMPs from Drosophila to reveal what AMPs are up to in vivo; by deleting single AMP genes, various combinations of genes, or all 14 genes the team was able to remove their corresponding AMPs to investigate how long their absence affected the fly’s resistance to different fungal and bacterial pathogens.

AMPs were found to work either together or by adding up their individual effects; and certain AMPs were found to be specific in defending against certain infections, highlighting a previously unknown level of specificity to the innate immune response.

By studying how these AMPs work it also can help us manage economically important insects whether it be protecting precious bumblebees or preventing annoying mosquitoes from spreading disease.

“Drosophila AMPs were found to act primarily against Gram negative bacteria and fungi to contribute additively or synergistically. In Remarkable specificity certain AMPs contribute the bulk of microbicidal activities against specific pathogens to provide functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.”

“Results may help us better understand how our own AMPs help to fight infection; it may be that some have defective copies of a specific AMP needed to prevent common infections putting them at higher risk. Fighting infection is great, but prevention is the ideal of medicine, which is what AMPs do, preventing infection before it ever settles in the first place” says Mark Austin Hanson.