Investigation of the molecular evolution of carbapenem resistance in Klebsiella quasipneumoniae

The evolution of multidrug resistance in Klebsiella species in response to selective pressure and the extent to which this may be reversible is not fully understood. The spread of carbapenem-resistant Enterobacteriaceae (CRE) is considered a public health threat. A combinational approach showed that epistatic changes are necessary for a Klebsiella resistant to multiple antibiotics to acquire a CRE phenotype. Evolution experiments demonstrated the fitness burden associated with antimicrobial resistance determinants, the reversion to a carbapenem-susceptible phenotype in an antibiotic-free environment, the importance of epistatic events and how variation in drug exposure can shape the evolutionary pathway to antibiotic resistance.