A pangenomic perspective on the emergence, maintenance, and predictability of antibiotic resistance

Abstract

The rapidly expanding number of sequenced bacterial strains and species, and the ongoing curation of bacterial pangenomes has uncovered unexpected complexities in understanding and addressing antibiotic resistance in the context of the pangenome. It is becoming apparent that differences in the genetic background can cause species and strain-specific responses to the same antibiotic, triggering differential selective pressures and thereby strain or species-specific adaptive outcomes. In this chapter, we consider how the pangenome, on a between and within species level, can affect the response to antibiotics and the development of resistance as well as the role selective pressures such as antibiotics play in shaping and maintaining the pangenome. We review the tools that are used to study antibiotic resistance within a pangenomic context, highlight recent findings, discuss strategies for predicting the emergence of resistance and consider how effective therapies can be developed in the context of the pangenome.