Decay and damage of therapeutic phage OMKO1 by environmental stressors

Abstract

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. Just as the effect of environmental conditions (e.g. elevated temperature) on antibiotic efficacy is well-studied, the effect of environmental stressors on the potency of phage therapy candidates demands examination. Therapeutic phage OMKO1 infects and kills the opportunistic human pathogen Pseudomonas aeruginosa. Here, we used phage OMKO1 as a model to test how environmental stressors can lead to damage and decay of virus particles. We assessed the effects of elevated temperatures, saline concentrations, and urea concentrations. We observed that OMKO1 particles were highly tolerant to different saline concentrations, but decayed more rapidly at elevated temperatures and under high concentrations of urea. Additionally, we found that exposure to elevated temperature reduced the ability of surviving phage particles to suppress the growth of P. aeruginosa, suggesting a temperature-induced damage. Our findings demonstrate that OMKO1 is highly tolerant to a range of conditions that could be experienced inside 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.

Stability study in selected conditions and biofilm-reducing activity of phages active against drug-resistant Acinetobacter baumannii

“…But therapeutic phage OMKO1 specific for P. aeruginosa showed stability in various concentrations of saline, even in 5 M saline for 90 min of incubation. 3 M and 4 M urea solutions caused a significant decrease in phage titer after 90 min of incubation 67 . This is a prime example for why it is so important to indicate under what conditions individual phages can maintain their therapeutic value.…”

Bacteriophage diet breadth is impacted by interactions between bacteria

“…Our results suggest numerous directions for future study. In the context of phage therapy, the performance of EH7 in minimal media emphasizes the necessity of testing how different environments affect phages and whether phage characteristics such as specificity tend to correlate with susceptibility to degradation [63]. These data also suggest that the ways bacteria modify their environments through alteration to local pH or vitamin concentrations may have consequences for the evolution and persistence of their viral predators.…”

“…Given previous observations that environmental factors such as salinity [63,64,65,66], pH [61,62,63], and metal presence can have significant impacts on phage titer [67,68,69], we attempted to identify the cause of degradation in our minimal media by removing one component at a time. We created minimal media without metals, without sulfur, without phosphorus, or some combination thereof.…”

Bacteriophage Effectively Rescues Pneumonia Caused by Prevalent Multidrug-Resistant Klebsiella pneumoniae in the Early Stage

“…These two highly efficient lytic phages can adequately inhibit bacteria growth in vitro . Human body temperatures can reach a maximum of 40°C, while phages could experience up to 50°C during storage and transportation ( 24 ). Both phages can maintain high activity from 37°C to 50°C.…”