How to build a super phage: Understanding and improving bacteriophage biocontrol of Pseudomonas syringae pathovars.

植物病原菌影响广泛的农业和园艺作物，并在世界范围内造成严重损失。从经济和科学的角度来看，丁香假单胞菌是一种主要的细菌病原体。紫丁香科和桑寄生致病变种引起李树(如樱桃、李子等)细菌性溃烂。据估计，英国水果生产每年损失超过50万GB。据预测，气候变化导致的强降雨和更高的气温将使情况变得更加糟糕。目前的广谱抗菌素控制策略，如使用抗生素和铜，由于它们对环境和人类健康的有害影响，以及由于将抗菌素耐药性传递给人类病原体的风险，正在被禁止。细菌种群的头号敌人是噬菌体，这是一种特定的病毒，能够劫持细菌细胞，在细胞裂解之前产生更多具有传染性的病毒粒子。然而，在开发有效的噬菌体生物防治之前，有几个因素需要考虑。噬菌体需要针对合适的病原菌菌株，它们需要在园艺环境中保持稳定，不应该竞争相同的寄主，并且应该能够避开细菌耐药性的出现。这个项目的目的是回答一个欺骗性的简单问题：是什么制造出一种有效的农业生防噬菌体鸡尾酒？我们将使用噬菌体和病原体的体外和体内共同进化结合基因组测序来组装植物中噬菌体和细菌病原体可能的进化结果。在计算机设计中，将通过结合不同噬菌体菌株的基因组特征，尝试利用噬菌体的生防潜力和稳定性来提高天然噬菌体的生防潜力。该项目将在植物中噬菌体和细菌之间的相互作用方面贡献重要的知识，可能改变我们对噬菌体生物防治的理解，其影响不仅限于假单胞菌。

Phytopathogenic bacteria affect a wide range of agricultural and horticultural crops and cause severe losses worldwide. Pseudomonas syringae pathovars are a major bacterial pathogen from an economic and scientific point of view. Pathovars syringae and morsprunorum cause bacterial canker on Prunus trees (e.g. cherry, plum...) with losses to UK fruit production estimated to above £500,000 every year. Severe rainfall and higher temperature due to climate change are predicted to make matters significantly worse. The current wide spectrum antimicrobial control strategies such as the use of antibiotics and copper are being banned due to their detrimental effects on environment, human health and due to the risk of passing antimicrobial resistance to human pathogens. The arch enemy of bacterial populations are bacteriophages, specific viruses that are able to hijack bacterial cells to produce more infectious virions before cell lysis. There are however several considerations before effective bacteriophage biocontrol can be developed. Phages need to target the right pathogen strains, they need to be stable in horticultural environment, should not compete for the same hosts, and should be able to evade emergence of bacterial resistance. The aim of this project is to answer a deceivingly simple question: What makes an effective biocontrol phage cocktail for agriculture? We will use in-vitro and in-vivo coevolution of phages and pathogens together with genome sequencing to assemble the possible evolutionary outcomes of phages and bacterial pathogens in planta. In silico design of bacteriophages will be then used to try to improve on biocontrol potential and stability of natural phages by combining genomic features of different phage strains. This project will contribute crucial knowledge on the interactions between phages, bacteria in plant that could transform our understanding of phage biocontrol with wide reaching impact beyond Pseudomonas spp.