Implications of stereochemistry in antibiotic resistance - the stereoselective metabolism of antibiotics by environmental bacteria

Antibiotic resistance (ABR) is recognised as a serious global health threat that is
most efficiently managed via a ‘one health’ approach which incorporates
environmental risk assessments. The environmental dimension of ABR in the past
has been largely overlooked, with recent studies underling the importance of nonclinical
settings in the emergence and spread of ABR. Despite this, a number of research gaps remain in regard to the drivers of ABR, these include the
development and fit-for-purpose environmental risk assessments for antibiotics.
Here we explore the implications of stereochemistry on the fate of antibiotics
within the environment and ABR. Molecular genetic approaches have greatly
increased our understanding of the evolution and spread of antibiotic resistance,
however there have been fewer studies on the dynamics of antibiotic-microbial
(A-M) interactions, especially with respect to stereochemistry. In order to address
this knowledge gap an interdisciplinary approach is required, along with the
development of sensitive and selective analytical tools. In order to address this a
novel approach for assaying bacterial resistance mechanisms in the context of AM
interactions was developed utilising a combination of traditional microbiology,
whole genome sequencing and analytical chemistry. Chloramphenicol was used to
provide a proof-of-concept to demonstrate stereoselective metabolism by resistant
environmental bacteria. Our data confirms that chloramphenicol can be
stereoselectively transformed by environmental bacteria, possibly due to due to
the lack of historical exposure to one enantiomer.