PT  - JOURNAL ARTICLE
AU  - Rosanna C. T. Wright
AU  - Ville-Petri Friman
AU  - Margaret C. M. Smith
AU  - Michael A. Brockhurst
TI  - Functional diversity increases the efficacy of phage combinations
AID  - 10.1101/2021.07.09.451746
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.09.451746
4099  - http://biorxiv.org/content/early/2021/07/09/2021.07.09.451746.short
4100  - http://biorxiv.org/content/early/2021/07/09/2021.07.09.451746.full
AB  - Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from 1 to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximised at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.Competing Interest StatementThe authors have declared no competing interest.T4PType IV PilusLPSLipopolysaccharide