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Stereoselective Bacterial Metabolism of Antibiotics in Environmental Bacteria – A Novel Biochemical Workflow

Although molecular genetic approaches have greatly increased our understanding of the evolution and spread of antibiotic resistance genes, there are fewer studies on the dynamics of antibiotic – bacterial (A-B) interactions, especially with respect to stereochemistry. Addressing this knowledge gap r...

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Detalles Bibliográficos
Autores principales: Elder, Felicity C. T., Feil, Edward J., Pascoe, Ben, Sheppard, Samuel K., Snape, Jason, Gaze, William H., Kasprzyk-Hordern, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086513/
https://www.ncbi.nlm.nih.gov/pubmed/33935981
http://dx.doi.org/10.3389/fmicb.2021.562157
Descripción
Sumario:Although molecular genetic approaches have greatly increased our understanding of the evolution and spread of antibiotic resistance genes, there are fewer studies on the dynamics of antibiotic – bacterial (A-B) interactions, especially with respect to stereochemistry. Addressing this knowledge gap requires an interdisciplinary synthesis, and the development of sensitive and selective analytical tools. Here we describe SAM (stereoselective antimicrobial metabolism) workflow, a novel interdisciplinary approach for assessing bacterial resistance mechanisms in the context of A-B interactions that utilise a combination of whole genome sequencing and mass spectrometry. Chloramphenicol was used to provide proof-of-concept to demonstrate the importance of stereoselective metabolism by resistant environmental bacteria. Our data shows that chloramphenicol can be stereoselectively transformed via microbial metabolism with R,R-(-)-CAP being subject to extensive metabolic transformation by an environmental bacterial strain. In contrast S,S-(+)-CAP is not metabolised by this bacterial strain, possibly due to the lack of previous exposure to this isomer in the absence of historical selective pressure to evolve metabolic capacity.