Credit: P. Morgan/NRG

The widespread use of antibiotics has driven the emergence of drug-resistance mutations in bacteria. These mutations are commonly assumed to have a fitness cost in the absence of antibiotics. However, accumulating evidence, including a new study of Salmonella enterica subsp. enterica serovar Typhi (which is the causative agent of typhoid), shows that drug-resistance mutations can confer antibiotic-independent fitness advantages.

Baker et al. generated 11 strains of S. Typhi, each with 1–3 mutations in the targets of fluoroquinolone antibiotics (that is, the DNA gyrase GyrA and/or the DNA topoisomerase ParC) on an otherwise isogenic background. These mutations are found in clinical and laboratory isolates of fluoroquinolone-resistant S. Typhi, and the authors confirmed that their strains indeed showed marked drug resistance. To test the fitness effects in the absence of antibiotic treatment, the authors co-cultured each strain along with the drug-sensitive control strain in vitro for ~150 generations. They measured the resultant proportions of strains by using high-throughput sequencing to quantify mutant and wild-type allele frequencies. Crucially, six of the drug-resistant strains still had a fitness advantage over the control strain in the absence of antibiotic treatment.

If these results are applicable to physiological settings in vivo, then they would imply that intentionally avoiding antibiotic use may not result in drug-resistant strains being outcompeted by drug-sensitive strains. However, given that the fitness benefits conferred by the drug-resistance mutations are greatly enhanced in the presence of antibiotics, prudent use of antibiotics will remain a valuable strategy.