Decay and damage of therapeutic phage OMKO1 by environmental stressors

Abstract

13Antibiotic resistant bacterial pathogens are increasingly prevalent, driving the need for alternative 14 approaches to chemical antibiotics when treating infections. One such approach is bacteriophage 15 therapy: the use of bacteria-specific viruses that lyse (kill) their host cells. However, while the effect of 16 environmental conditions (e.g. elevated temperature) on antibiotic efficacy is well-studied, the 17 generalized effects of environmental stressors on the potency of phage therapy candidates are seldom 18 studied. Therapeutic phage OMKO1 infects and kills the opportunistic human pathogen Pseudomonas 19 aeruginosa, while selecting for the evolution of antibiotic re-sensitivity in the target bacterial 20population. Here, we used phage OMKO1 as a model to test how a therapeutic virus degrades in 21 different environments, and whether exposure to an environmental stressor affects subsequent growth 22 ability on host bacteria. We observed that OMKO1 particles were highly tolerant to different saline 23concentrations, but rapidly deactivated at elevated temperatures and under high concentrations of 24 urea. We also found that exposure to elevated temperature reduced the growth ability of surviving 25 OMKO1 particles, suggesting a temperature-induced phenotypic shift. Our findings demonstrate that 26 OMKO1 is highly tolerant to a range of conditions that could be experienced in and outside the human 27 body, while also showing the need for careful characterization of therapeutic phages to ensure that 28 environmental exposure does not compromise their expected potency, dosing, and pharmacokinetics. 29

Phenotypic flux: The role of physiology in explaining the conundrum of bacterial persistence amid phage attack

“…Population heterogeneity and density-dependent effects can be further influenced by environmental conditions , but I will only consider the direct effect of the environment on phage physiology via phage virion decay ( Wommack et al. 1996 ; Marianne and Taddei 2006 ; Blazanin et al. 2022 ).…”

“…1996 ; Wommack et al. 1996 ), inactivation by the immune system ( Dabrowska and Abedon 2019 ), or other stressors within the human body ( Blazanin et al. 2022 ).…”