Impact of stereochemistry of antimicrobial agents on their environmental fate, biological potency and the emergence of resistance

GSTDTAP

项目编号	NE/N019261/1
	Impact of stereochemistry of antimicrobial agents on their environmental fate, biological potency and the emergence of resistance
	[unavailable]
主持机构	University of Bath
项目开始年	2016
	2016-06-01
项目结束日期	2018-03-31
资助机构	UK-NERC
项目类别	Research Grant
国家	英国
语种	英语
英文摘要	This project aims to understand and address the impact of stereoisomerism of antimicrobial agents in their environmental cycle on mechanisms behind the development of antimicrobial resistance. The risk of promotion of antibiotic resistant bacteria is by far the greatest human health concern with regards to medicinal products in the environment. The continuous introduction of sub-inhibitory quantities of antimicrobial agents (AAs) to the environment is believed to be directly linked with antimicrobial resistance (AMR). Unfortunately, there is little knowledge of mechanisms in the environment and influencing factors due to the multi-dimensional nature of the AMR problem. There are several research gaps that need to be addressed including research into contaminated habitats (e.g. wastewater) where AAs, co-selecting agents, bacteria carrying resistance determinants and favourable conditions for bacterial growth prevail at the same time. Furthermore, the stereochemistry of AAs (which is key in defining their biological potency) has never been studied in the context of their environmental fate and effects. This is an oversight as changes in stereoisomeric profile of AAs throughout their environmental cycle will lead to (and be influenced by) changes in the composition and structure of microbial communities present in the environment. This might further contribute to the development of AMR, a phenomenon that has never been the subject of investigation in the context of stereochemistry of AAs. This project postulates that stereochemistry of AAs determines their environmental fate and biological effects. It also hypothesizes that two enantiomers of the same AA should be recognised as two different substances that can elicit different responses leading to changes in the environmental fate and effects of the drug. The project will: 1. Verify the mechanisms of (stereoselective) transformation of chiral antimicrobial agents and their metabolites during wastewater treatment and in receiving waters 2. Identify resistant bacterial taxa responsible for (stereoselective) degradation of antimicrobial agents and to study the development of antimicrobial resistance at stereoisomeric level 3. Recommend changes to ERA via inclusion of AAs (and their stereochemistry) and ARGs as AMR indicators The stereochemistry of AAs is complex, as many of the semi-synthetic agents are marketed as mixtures of diastereomers and a number of synthetic agents are used as racemates. In this project we will focus on ofloxacin and chloramphenicol, but we will also consider other synthetic quinolones, Beta-lactams (e.g. amoxicillin) and carbapenems (e.g. meropenem). Considering the importance of better understanding environmental and human health impacts from chiral pollutants such as AAs and the need for the development of new solutions tackling AMR, this project has the potential to lead to groundbreaking research with long term scientific, technological and societal impact.
来源学科分类	Natural Environment Research
文献类型	项目
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/86206
专题	环境与发展全球科技态势
推荐引用方式 GB/T 7714	[unavailable].Impact of stereochemistry of antimicrobial agents on their environmental fate, biological potency and the emergence of resistance.2016.