An environmental metabolomics investigation of the effects of chiral pharmaceuticals and environmental pollutants on microorganisms

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Abstract

Active pharmaceutical ingredients (APIs) and their metabolites are ubiquitous in the environment and their occurrence in the aquatic environment is of growing concern. However, despite the fact that these may cause harmful effects in organisms found within this niche, little is currently known about the effects of APIs in the aquatic environment. Chiral pharmaceuticals are of particular concern as the enantiomers may be metabolised differently, with the potential for the production of an array of harmful compounds. There are many racemic APIs for treating human and animal conditions, and even in these target organisms the pharmacodynamic effects of the enantiomers are not always known. Within recent years the importance of the interactions of these compounds within the aquatic environment has been realised and information regarding the fate and biodegradation of such environmental pollutants is of great importance. The advent of post-genomic technologies has proved advantageous in the study of the effects of these environmental pollutants. In this thesis, the effects of a range of chiral APIs, and other environmental pollutants, on environmentally relevant microorganisms were investigated at the metabolome level. The effects of chiral APIs were investigated in a number of prokaryotic and eukaryotic systems in order to provide a comprehensive study of the effects of the APIs in the aquatic environment. FT-IR spectroscopy was employed for metabolic fingerprinting of some environmentally relevant bacteria and GC-MS was subsequently employed for metabolite profiling of two pseudomonads that had shown differential chiral effects with Propranolol. In addition, FT-IR microspectroscopy was employed for the investigation of the phenotypic and localised effects of chiral APIs in a eukaryotic system. Furthermore, the effects of a range of environmental pollutants on a complex bacterial community were investigated with the use of FT-IR spectroscopy and multivariate analysis. Initial results indicated a large phenotypic response in relation to phenol, and this was further explored with a range of ageing experiments and metabolic fingerprinting. An FT-IR peak was found to be characteristic of the phenotypic changes in the actively degrading communities and this was likely to be a degradation product of phenol, and armed with this knowledge the activated sludge community was monitored during the active degradation of phenol with the use of GC-MS.The work presented in this thesis has shown for the first time that metabolomics allows subtle phenotypes in microorganisms to be revealed when they are exposed to chiral forms of APIs which are commonly found in the aquatic environment. Despite these APIs not being designed for any interaction with bacteria and aquatic life in general these are significant findings and may have implications as more and more APIs become detectable and concentrated in the environment due to continued use in man and indeed animals or aquaculture.

Keyword(s)

environment; metabolomics

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