Fitness gains hamper efforts to tackle drug resistance

Abstract

It has long been assumed that resistance to antibiotics reduces the fitness of disease-causing bacteria, but experiments on Salmonella Typhi, the bacteria that causes Typhoid fever, are now challenging this view.

Keywords: Salmonella; antibiotic resistance; epistasis; fitness cost; fluoroquinolone; typhoid.

Figure 1.. Fluoroquinolone-resistant mutants of Salmonella Typhi vs susceptible strains.

Fluoroquinolone-resistant mutants (red) with either one, two or three mutations in the gyrA and parC genes were cultured with a fluoroquinolone-susceptible parent strain (white) in liquid media that did not contain any antibiotics. Every 24 hr, over a period of 15 days, these growth cultures were subcultured into fresh antibiotic-free media, and samples were taken for colony counting and DNA extraction. Pyrosequencing of extracted DNA was used to determine the frequency of each mutation and the parent strain at each time-point, and to calculate the fitness of each mutant compared to the parent strain. Increases in fitness allowed some single and double mutants (red arrow) outcompeted the parent strain, while a reduction in fitness meant that the triple mutant lost out to the parent strain (blue arrow).