Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
2019
All animals – from humans to mice, jellyfish to fruit flies – are armed with an immune system to defend against infections. The immune system’s first line of defence often involves a group of short proteins called antimicrobial peptides. These proteins are found anywhere that germs and microbes come into contact with the body, including the skin, eyes and lungs. In many cases, it is unclear how individual antimicrobial peptides work. For example, which germs are they most effective against? Do they work alone, or in a mixture of other antimicrobial peptides? To learn more about a protein, scientists can often delete the gene that encodes it and observe what happens. Antimicrobial peptides, however, are small proteins encoded by a large number of very short genes, which makes them difficult to target with most genetic tools. Fortunately, gene editing via the CRISPR/Cas9 system can overcome many of the limitations of more traditional methods; this allowed Hanson et al. to systematically remove the antimicrobial peptide genes from fruit flies to explore how these proteins work. In the experiments, all 14 antimicrobial peptide genes known from fruit flies were removed, and the flies were then infected with a variety of bacteria and fungi. Hanson et al. found that the antimicrobial peptides were effective against many bacteria, but unexpectedly they were far more important for controlling one general kind of bacterial infection, but not another kind. Further experiments showed that some of these proteins work alone, targeting only a particular species of microbe. This finding suggested that animals might fight infections by very specific bacteria with a very specific antimicrobial peptide rather than with a mixture. By understanding how antimicrobial peptides work in more detail, scientists can learn what types of microbes they are most effective against. In the future, this information may eventually lead to the development of new types of antibiotics and better management of diseases that affect important insects, like bumblebees.
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