Antibiotic resistance is an increasing threat to global health, with the UK chief medical officer Dame Sally Davis recently stating “If we don’t take action, then we may all be back in an almost 19th Century environment where infections kill us as a result of routine operations.” This makes research into antibiotic resistance more relevant than ever. A recent study published in BMC Evolutionary Biology by Daniel Angst and Alex Hall from the ETH Zurich, Switzerland looks at how antibiotic resistant bacteria evolve when antibiotics are removed from their environment.
The development of antibiotic resistance in bacteria generally has a cost to be paid in terms of their fitness. As such it is often assumed that over generations in the absence of the selective pressure of an antibiotic, resistance is lost due to its detrimental cost on fitness. This situation is complicated by studies now suggesting that the fitness cost of antibiotic resistance may be altered by the development of other resistance mutations. Angst and Hall probed the complexity of this scenario by experimentally evolving antibiotic resistant and antibiotic sensitive strains of E.coli in an antibiotic free environment for 200 generations and looking at the effect on fitness of introducing additional streptomycin resistance alleles into the strains before and after evolution in the antibiotic free medium.
They found that the detrimental effects of antibiotic resistance on fitness were reduced in strains that had evolved in the antibiotic free medium. This suggests that the occurrence of beneficial mutations incorporated during evolution in antibiotic free medium are able to buffer the cost of antibiotic resistance. The history of the evolution of a bacterial strain therefore effects the future evolution of antibiotic resistance and its persistence. This robust study adds strong evidence to previous studies showing the epistatic nature of antibiotic resistance.
The evidence presented in this experimental study has potential relevance when looking at the fitness cost of antibiotic resistance in real populations of disease causing bacteria. It is particularly relevant to chronic infections such as those in cystic fibrosis patients, in which the bacteria have many generations to potentially fix mutations in the absence of antibiotics. If it is the case that these mutations mitigate the cost of antibiotic resistance then research looking at the epistasis between resistance elements and other types of mutations will be important in predicting how likely it is that multi-drug resistant bacteria will remain after different treatments for infection.