Fitness costs of antibiotic resistance mutations in rich media do not reliably predict those in infection-like environments
The acquisition of antibiotic resistance is typically associated with a fitness cost, reducing the competitive ability of cells in the absence of antibiotics. Our ability to predict these costs informs our ability to predict how likely it is that resistance will subside in the absence of treatment. Fitness costs are typically measured in laboratory cultures using a nutritionally rich medium for…
Antibiotic resistance mutations in Pseudomonas aeruginosa often come with a fitness cost, making the bacteria less competitive when antibiotics aren't present. Predicting these costs helps predict how resistance might decrease without treatment. Traditionally, these costs are measured in laboratory cultures using a nutrient-rich medium. However, a new study explored how infection-like environments affect the prevalence and severity of these fitness costs in the opportunistic pathogen P. aeruginosa.
The researchers examined two clinically relevant infection niches: the lung and urinary tract. They used infection-niche mimicking media to model the chemical compositions of these environments. The results showed that fitness costs of resistance mutations in rich media did not accurately predict those in infection-like environments. On average, costs were higher in the lung-mimicking environment, and costly mutations were less common in the urinary tract-mimicking environment.
The study used synthetic human urine to enhance the fitness of P. aeruginosa with resistance mutations in nfxB, a gene encoding a multidrug efflux pump transcriptional repressor. The researchers identified oxalate as the likely component driving this effect. The findings underscore the importance of environmental chemical composition in shaping the fitness costs of resistance in P. aeruginosa. Additionally, the study suggests that nfxB mutants might have a selective advantage in the urinary tract, where oxalate is present.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
