Chairs: Rowan Casey and David Mark

Global health is increasingly threatened by antibiotic resistance, reducing our ability to treat infectious diseases, leading to increased morbidity and mortality. Antibiotic resistance mutations are often thought to incur a fitness cost, reflected in reduced competitive ability without antibiotics. These costs are thought to represent a major obstacle to the spread of resistance on an epidemiological scale. We investigated whether microbial interactions influence the fitness costs of antibiotic resistance mutations in the opportunistic bacterial pathogen Pseudomonas aeruginosa. A large-scale screen of over 400 fitness assays was used to characterise the fitness of spontaneous resistance mutations in P. aeruginosa, using a library of 36 mutants and 12 human microbiome bacterial and fungal species. The fitness of antibiotic-resistant mutants was assessed in co-culture compared to monoculture conditions, revealing that most resistance mutation and microbial interaction combinations did not significantly alter fitness. Mutants exhibited significant fitness differences in only 16% of fitness assays driven by microbial interactions; 5% showed increased fitness and 11% showed decreased fitness. Fitness differences were most often associated with mutations related to efflux regulation and cell wall synthesis. Efflux regulation mutants demonstrated a mixed fitness response depending on the microbe, with equal increases and decreases in fitness. These context-dependent fitness costs will be further explored to better understand the interactions underlying these variations. Understanding the factors that influence fitness costs associated with resistance is crucial for predicting the likelihood of newly emerged resistance mutations spreading and, ultimately, could lead to novel strategies for combating resistance by manipulating these costs.