The biological cost of mutational antibiotic resistance: any practical conclusions?
A key parameter influencing the rate and trajectory of the evolution of antibiotic resistance is the fitness cost of resistance. Recent studies have demonstrated that antibiotic resistance, whether caused by target alteration or by other mechanisms, generally confers a reduction in fitness expressed as reduced growth, virulence or transmission. These findings imply that resistance might be reversible, provided antibiotic use is reduced. However, several processes act to stabilize resistance, including compensatory evolution where the fitness cost is ameliorated by additional mutation without loss of resistance, the rare occurrence of cost-free resistance mechanisms and genetic linkage or co-selection between the resistance markers and other selected markers. Conceivably we can use this knowledge to rationally choose and design targets and drugs where the costs of resistance are the highest, and where the likelihood of compensation is the lowest.
Andersson
Dan I
DI
Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, S-751 23 Uppsala, Sweden. Dan.Andersson@imbim.uu.se
D000222:Adaptation, Physiological; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D018407:Bacterial Physiological Phenomena; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000187:drug effects*; D014774:Virulence
D000900:Anti-Bacterial Agents