Methods to Determine Mutational Trajectories After Experimental Evolution of Antibiotic Resistance

Douglas L Huseby; Diarmaid Hughes

doi:10.1007/978-1-4939-7638-6_9

Methods to Determine Mutational Trajectories After Experimental Evolution of Antibiotic Resistance

Methods Mol Biol. 2018:1736:95-103. doi: 10.1007/978-1-4939-7638-6_9.

Authors

Douglas L Huseby¹, Diarmaid Hughes²

Affiliations

¹ Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
² Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Diarmaid.hughes@imbim.uu.se.

PMID: 29322462
DOI: 10.1007/978-1-4939-7638-6_9

Abstract

The evolution of bacterial resistance to antibiotics by mutation within the genome (as distinct from horizontal gene transfer of new material into a genome) could occur in a single step but is usually a multistep process. Resistance evolution can be studied in laboratory environments by serial passage of bacteria in liquid culture or on agar, with selection at constant, or varying, concentrations of drug. Whole genome sequencing can be used to make an initial analysis of the evolved mutants. The trajectory of evolution can be determined by sequence analysis of strains from intermediate steps in the evolution, complemented by phenotypic analysis of genetically reconstructed isogenic strains that recapitulate the intermediate steps in the evolution.

Keywords: Isogenic strains; Minimal inhibitory concentration; Relative fitness; Serial passage; Whole genome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects*
Bacteria / genetics*
DNA Mutational Analysis* / methods
Drug Resistance, Bacterial*
Genome, Bacterial
Microbial Sensitivity Tests*
Mutation*
Whole Genome Sequencing

Substances

Anti-Bacterial Agents