De novo acquisition of antibiotic resistance in six species of bacteria

Bacteria can become resistant to antibiotics in two ways, by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole genome sequencing (WGS) sequencing at two time points of the evolutionary trajectory. In this study, we found: 1) all of the six strains can develop high levels of resistance against most antibiotics. 2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination. 3) the number of mutations varies widely, with Y. enterocolitica having by far the most. 4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species. 5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes.