In the advanced online edition of Molecular Biology and Evolution, Oz, et. al., utilized an experimental evolution approach to evolve 88 different E. coli populations against 22 antibiotics, under "strong" and "mild" selection conditions. After 21 days, they isolated bacterial clones, measured the resistance to each antibiotic, and performed whole-genome sequencing of resistance clones to tease out the genetic changes that could be responsible for antibiotic resistance.
Their results demonstrate that the evolution of cross-resistance depends on selection strength. Overall, they found evidence for higher cross-resistance in the strongly selected strains and higher numbers of pathway-specific mutations. The study yielded important new insights into the increased emergence of drug resistance with the use of high doses of antibiotics, as well as hypersensitivities to exploit for new antibiotic therapies.