Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, United States of America.
Program in Microbiology, Yale School of Medicine, New Haven, CT, United States of America.
PLoS One. 2022 Feb 23;17(2):e0263887. doi: 10.1371/journal.pone.0263887. eCollection 2022.
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.
耐药细菌病原体日益流行,这促使人们在治疗感染时需要寻找化学抗生素的替代方法。其中一种方法是噬菌体疗法:利用特异性杀死宿主细胞的细菌病毒。正如环境条件(例如高温)对抗生素疗效的影响得到了充分研究一样,环境应激源对噬菌体治疗候选物效力的影响也需要进行研究。治疗性噬菌体 OMKO1 可感染并杀死机会性人类病原体铜绿假单胞菌。在这里,我们使用噬菌体 OMKO1 作为模型来测试环境应激源如何导致病毒颗粒的损伤和衰变。我们评估了高温、盐度和尿素浓度的影响。我们观察到,OMKO1 颗粒对不同盐度具有很高的耐受性,但在高温和高浓度尿素下衰变得更快。此外,我们发现暴露于高温会降低存活噬菌体颗粒抑制铜绿假单胞菌生长的能力,这表明存在温度诱导的损伤。我们的研究结果表明,OMKO1 对人体内外可能遇到的一系列条件具有高度耐受性,同时也表明需要仔细表征治疗性噬菌体,以确保环境暴露不会影响其预期效力、剂量和药代动力学。