Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs.
Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.
Cherkasov
Artem
A
Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, British Columbia V6T 1Z3, Canada.
Hilpert
Kai
K
Jenssen
Håvard
H
Fjell
Christopher D
CD
Waldbrook
Matt
M
Mullaly
Sarah C
SC
Volkmer
Rudolf
R
Hancock
Robert E W
RE
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001185:Artificial Intelligence; D003198:Computer Simulation; D015195:Drug Design; D004352:Drug Resistance, Microbial; D006801:Humans; D051379:Mice; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity
D000900:Anti-Bacterial Agents; D019151:Peptide Library; D010455:Peptides