title: Differential epigenetic compatibility of qnr antibiotic resistance determinants with the chromosome of Escherichia coli.
abstract: Environmental bacteria harbor a plethora of genes that, upon their horizontal transfer to new hosts, may confer resistance to antibiotics, although the number of such determinants actually acquired by pathogenic bacteria is very low. The founder effect, fitness costs and ecological connectivity all influence the chances of resistance transfer being successful. We examined the importance of these bottlenecks using the family of quinolone resistance determinants Qnr. The results indicate the epigenetic compatibility of a determinant with the host genome to be of great importance in the acquisition and spread of resistance. A plasmid carrying the widely distributed QnrA determinant was stable in Escherichia coli, whereas the SmQnr determinant was unstable despite both proteins having very similar tertiary structures. This indicates that the fitness costs associated with the acquisition of antibiotic resistance may not derive from a non-specific metabolic burden, but from the acquired gene causing specific changes in bacterial metabolic and regulatory networks. The observed stabilization of the plasmid encoding SmQnr by chromosomal mutations, including a mutant lacking the global regulator H-NS, reinforces this idea. Since quinolones are synthetic antibiotics, and since the origin of QnrA is the environmental bacterium Shewanella algae, the role of QnrA in this organism is unlikely to be that of conferring resistance. Its evolution toward this may have occurred through mutations or because of an environmental change (exaptation). The present results indicate that the chromosomally encoded Qnr determinants of S. algae can confer quinolone resistance upon their transfer to E. coli without the need of any further mutation. These results suggest that exaptation is important in the evolution of antibiotic resistance.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Cantoblanco, Madrid, Spain.
authors.forename: María B
authors.initials: MB
authors.lastname: Sánchez
authors.forename: José L
authors.initials: JL
authors.lastname: Martínez
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002876:Chromosomes, Bacterial / Q000187:drug effects / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D022761:Gene Transfer, Horizontal / Q000187:drug effects / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D015363:Quinolones / Q000494:pharmacology*; D020592:Shewanella / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015363:Quinolones