The impact of temperature on host-parasite interactions and co-evolution

由于抗生素在医药和农业中的普遍过度使用，抗菌素耐药性是一个日益严重的全球威胁。这促使人们研究治疗细菌感染的替代方法。一个有希望的候选者是噬菌体，这是一种针对并杀死细菌病原体的病毒。虽然噬菌体在实验室条件下和临床试验中都证明了抑制细菌的能力，但噬菌体的研究通常忽略了环境应激，包括温度变化对细菌-噬菌体相互作用的影响。噬菌体疗法预计将在哺乳动物宿主内(正常体温与感染引起的发烧)和宿主之间(人类与各种牲畜)经历广泛的温度范围。然而，目前尚不清楚噬菌体的活性是在不同温度下保持、促进还是限制。这个项目的总体目标是研究温度如何调节细菌和噬菌体之间的相互作用。具体地说，该项目的目的是：一)调查温度对噬菌体活性的影响；二)确定是否可以通过实验进化噬菌体，以提高其在不同温度下的活性；三)评估温度对细菌和噬菌体之间协同进化的影响。利用条件致病菌铜绿假单胞菌和各种裂解噬菌体，这个项目将提高我们对哺乳动物宿主内部和之间的体温变化如何影响噬菌体治疗或微生物体内自然的细菌-噬菌体相互作用的理解。此外，它还将确定温度变化是否限制或促进细菌对噬菌体的抗性进化。这一项目的发现将对选择和应用噬菌体治疗细菌感染具有重要意义。鉴于该项目在解决抗生素耐药性、治疗细菌感染和评估体温变化对人类“噬菌体”的潜在影响方面的相关性，BBSRC的优先事项包括：1.抗击抗菌素耐药性2.动物健康3.综合微生物组研究

Antimicrobial resistance is a growing global threat because of widespread antibiotic overuse in medicine and agriculture. This has prompted investigations into alternative methods for the treatment of bacterial infections. A promising candidate is bacteriophages (phages), viruses which target and kill bacterial pathogens. While the ability of phages to repress bacteria has been demonstrated under both lab conditions and in clinical trials, phage studies have generally neglected the impact of environment stresses, including variation in temperature, on bacteria-phage interactions. Phage therapies are expected to experience broad temperature ranges both within mammalian hosts (normal body temperature vs infection-induced fevers) and between hosts (humans vs assorted livestock). However, it is unclear whether phage activity is maintained, promoted, or restricted across temperatures. The overall goal of this project is to investigate how temperature mediates interactions between bacteria and phage. Specifically, this project aims to i) investigate the impact of temperature on phage activity; ii) determine whether phages can be evolved experimentally to improve their activity across temperatures; and iii) assess the impact of temperature on co-evolution between bacteria and phages. Using the opportunistic pathogen Pseudomonas aeruginosa and a diversity of lytic phages, this project will improve our understanding of how variation in body temperature both within and between mammalian hosts affects phage treatments or bacteria-phage interactions naturally within the microbiome. Further, it will determine whether changes in temperatures restrict or facilitate the evolution of bacterial resistance to phage. The findings of this project will have important implications for the selection and application of phages to treat bacterial infections.Given the relevance of this project both in tackling antibiotic resistance, treating bacterial infections, and assessing the potential impact of changes in body temperature on the human "phageome", the BBSRC priorities addressed include:1. Combatting antimicrobial resistance2. Animal health3. Integrative microbiome research