The host as a selective pressure: interactions of immunity, AMR, and persistence

该项目的目标是了解宿主免疫反应所施加的选择如何改变细菌生物学。我们将用相对温和的细菌病原体感染果蝇，并跟踪感染细菌的表型和基因型变化。我们将比较在野生型宿主中进化的细菌和在缺乏特定免疫功能的宿主中进化的细菌。然后，我们将交叉关联我们在致病活性中观察到的变化与其他相关表型（持久性形成，抗菌素耐药性）的变化，以了解与非人类宿主的相互作用如何改变微生物生物学的基本方面。鉴于昆虫免疫反应对抗菌肽的强烈依赖以及抗菌肽与其他感兴趣的药物之间的交叉耐药的潜力，这一点特别有趣。

The goal of this project is to understand how the selection imposed by host immune responses changes bacterial biology. We will infect fruit flies with relatively mild bacterial pathogens and track phenotypic and genotypic change in infecting bacteria. We will compare bacteria evolved in wild-type hosts to those evolved in hosts lacking specific aspects of immune function. We will then cross-correlate the changes we observe in pathogenic activity with changes in other related phenotypes (persister formation, antimicrobial resistance) to develop an understanding of how the interaction with non-human hosts can change fundamental aspects of microbial biology. This is of particular interest given the strong reliance of insect immune responses on antimicrobial peptides and the potential for cross-resistance between antimicrobial peptides and other drugs of interest.