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In vitro and in vivo evaluation of the biofilm-degrading Pseudomonasphage Motto, as a candidate for phage therapy

Prasanth Manohar, Belinda Loh, Dann Turner, Tamizhselvi Ramasamy, Marimuthu Mathankumar, Namasivayam Elangovan, Ramesh Nachimuthu, Sebastian Leptihn

https://www.biorxiv.org/content/10.1101/2022.10.12.512010v1

Abstract

Infections caused by Pseudomonas aeruginosa are becoming increasingly difficult to treat due to the emergence of strains that have acquired multidrug resistance. Therefore, phage therapy has gained attention as an alternative to the treatment of pseudomonal infections. Phages are not only bactericidal but occasionally show activity against biofilm as well. Here, we describe the Pseudomonas phage Motto which has the ability to clear P. aeruginosainfections in an animal model and also exhibited biofilm-degrading properties. The phage has substantial antibiofilm activity against strong biofilm-producing isolates (n = 10), with at least a 2-fold reduction within 24 hours. To demonstrate the safety of using phage Motto, we performed cytotoxicity studies with human cell lines (HEK 293 and RAW 264.7 macrophages). Using a previously established in vivo model, we demonstrated the efficacy of Motto in C. elegans, with a 90% survival rate when treated with the phage at an MOI of 10.