Understanding the Spread of Antibiotic Resistance Through Mobile Genetic Elements in Bacterial Populations

通过细菌种群中的移动遗传元件了解抗生素耐药性的传播

• 批准号: 2887832
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2887832
• 关键词: Understanding; Spread; Antibiotic; Resistance; Through

The growing threat of Antimicrobial Resistance (AMR) is predicted to cause the death of 10 million people annually by 2050. The remarkable ability of bacteria to rapidly acquire resistance to antibiotics is a major challenge for healthcare professionals and the pharmaceutical industry. Even when it is possible to treat infections caused by multi-drug resistant pathogens, it can be difficult and expensive, and there is a dearth of new antimicrobials coming to market owing to rapid emergence of resistance in the face of prolonged development and testing. Preventing the emergence of AMR in potential pathogens is therefore an important goal for evolutionary microbiology. Mobile genetic elements (MGEs) such as plasmids and transposable elements are key driving forces that transmit AMR within bacterial communities. While plasmids are expected to be lost when there is low or no selection pressures, plasmids containing AMR genes are known to persist in environments with low, or even no, antibiotic selection pressure (low antibiotic concentration). It is thought that the ability of AMR plasmids to persist in communities is due to the presence of bacteria that can act as reservoirs for plasmids, because different bacteria vary in their susceptibility to acquiring, harbouring, and disseminating resistance MGEs. However, the features of bacteria that predispose them to become plasmid reservoirs is unclear, hampering our ability to predict such behaviour and develop therapeutic treatments to efficiently tackle AMR.I will be working on studying the susceptibility of bacteria towards MGEs, and asking: what genetic and molecular factors stabilise plasmids in the host? What causes the ability to differentially acquire plasmids? And what evolutionary forces stabilise these interactions? My project will focus on the interactions between diverse strains of the opportunistic pathogen Pseudomonas aeruginosa, and their associated MGEs. I will be combining wet-lab experiments with Machine Learning and Bioinformatics tools to study plasmid dynamics as a function of the genetic interaction between the plasmid and the host genome. This work will help identify the underlying mechanisms that allow plasmids to persist and transfer among members of bacterial communities. Ultimately, we will be able to predict microbiomes in which transmission of AMR plasmids are likely to be heightened, allowing us to better control the spread of antimicrobial resistance.

预计到2050年，抗菌耐药性（AMR）的威胁日益增长会导致1000万人死亡。细菌迅速获得对抗生素的耐药性的显着能力是医疗保健专业人员和制药行业的主要挑战。即使可以治疗由多药耐药病原体引起的感染，它也可能很困难且昂贵，并且由于面对延长的开发和测试，由于耐药性的迅速出现，因此缺乏新的抗菌剂。因此，预防潜在病原体中AMR的出现是进化微生物学的重要目标。移动遗传因素（MGE），例如质粒和转座元素是将AMR传播在细菌群落中的关键驱动力。虽然预计质粒在低或没有选择压力时会丢失，但已知包含AMR基因的质粒在低（甚至没有抗生素选择压力）（低抗生素浓度）的环境中持续存在。人们认为，AMR质粒在群落中持续存在的能力是由于存在可作为质粒的储存剂的存在所致，因为不同的细菌在其获取，携带和传播耐药性测量的敏感性方面有所不同。然而，易感性的细菌特征尚不清楚，阻碍了我们预测这种行为并发展治疗方法以有效解决AMR的能力。我将致力于研究细菌对MGE的敏感性，并问：什么遗传和分子因素稳定宿主中的遗传因素稳定质生？是什么原因导致差异获得质粒的能力？哪些进化力稳定了这些相互作用？我的项目将集中于机会性病原体假单胞菌的各种菌株及其相关的MGE之间的相互作用。我将将湿的实验与机器学习和生物信息学工具相结合，以研究质粒动力学，这是质粒与宿主基因组之间遗传相互作用的函数。这项工作将有助于确定允许质粒在细菌群落成员之间持续和转移的潜在机制。最终，我们将能够预测微生物组，在这种微生物中，AMR质粒的传播可能会增强，从而使我们能够更好地控制抗微生物耐药性的传播。