PT  - JOURNAL ARTICLE
AU  - Michael Blazanin
AU  - Wai Tin Lam
AU  - Benjamin K. Chan
AU  - Paul E. Turner
TI  - Characterizing the tolerance of phage therapy candidate OMKO1 to environmental stress
AID  - 10.1101/864025
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 864025
4099  - http://biorxiv.org/content/early/2019/12/03/864025.short
4100  - http://biorxiv.org/content/early/2019/12/03/864025.full
AB  - Antibiotic resistant bacterial pathogens are increasingly prevalent, driving the need for alternative approaches to chemical antibiotics when treating infections. One such approach is bacteriophage therapy: the use of bacteria-specific viruses that lyse (kill) their host cells. However, while the effect of environmental conditions (e.g. elevated temperature) on antibiotic efficacy is well-studied, the generalized effects of environmental stressors on the potency of phage therapy candidates are seldom studied. Therapeutic phage OMKO1 infects and kills the opportunistic human pathogen Pseudomonas aeruginosa, while selecting for the evolution of antibiotic re-sensitivity in the target bacterial population. Here, we used phage OMKO1 as a model to test how a therapeutic virus degrades in different environments, and whether exposure to an environmental stressor affects subsequent growth ability on host bacteria. We observed that OMKO1 particles were highly tolerant to different saline concentrations, but rapidly deactivated at elevated temperatures and under high concentrations of urea. We also found that exposure to elevated temperature reduced the growth ability of surviving OMKO1 particles, suggesting a temperature-induced phenotypic shift. Our findings demonstrate that OMKO1 is highly tolerant to a range of conditions that could be experienced in and outside the human body, while also showing the need for careful characterization of therapeutic phages to ensure that environmental exposure does not compromise their expected potency, dosing, and pharmacokinetics.