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

由于抗生素在医学和农业中的广泛过度使用，抗生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，一种靶向并杀死细菌病原体的病毒。虽然在实验室条件和临床试验中已经证明了噬菌体抑制细菌的能力，但噬菌体研究通常忽略了环境应力（包括温度变化）对细菌-噬菌体相互作用的影响。预期噬菌体疗法在哺乳动物宿主内（正常体温与感染诱导的发热）和宿主之间（人类与各种牲畜）经历宽的温度范围。然而，目前还不清楚噬菌体活性是否在不同温度下保持、促进或限制。该项目的总体目标是研究温度如何介导细菌和噬菌体之间的相互作用。具体而言，该项目旨在i）研究温度对噬菌体活性的影响; ii）确定噬菌体是否可以通过实验进化以提高其在不同温度下的活性; iii）评估温度对细菌和噬菌体之间共同进化的影响。利用机会致病菌铜绿假单胞菌和多种裂解酶，该项目将提高我们对哺乳动物宿主内和宿主之间体温变化如何影响噬菌体治疗或微生物组内细菌-噬菌体相互作用的理解。此外，它将确定温度的变化是否限制或促进细菌对噬菌体的抗性的进化。该项目的研究结果将对抗生素耐药性的选择和应用具有重要意义。考虑到该项目在解决抗生素耐药性、治疗细菌感染以及评估体温变化对人类“噬菌体组”的潜在影响方面的相关性，BBSRC优先考虑的问题包括：1.对抗抗菌素耐药性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