title: Genomics of adaptation during experimental evolution of the opportunistic pathogen Pseudomonas aeruginosa.
abstract: Adaptation is likely to be an important determinant of the success of many pathogens, for example when colonizing a new host species, when challenged by antibiotic treatment, or in governing the establishment and progress of long-term chronic infection. Yet, the genomic basis of adaptation is poorly understood in general, and for pathogens in particular. We investigated the genetics of adaptation to cystic fibrosis-like culture conditions in the presence and absence of fluoroquinolone antibiotics using the opportunistic pathogen Pseudomonas aeruginosa. Whole-genome sequencing of experimentally evolved isolates revealed parallel evolution at a handful of known antibiotic resistance genes. While the level of antibiotic resistance was largely determined by these known resistance genes, the costs of resistance were instead attributable to a number of mutations that were specific to individual experimental isolates. Notably, stereotypical quinolone resistance mutations in DNA gyrase often co-occurred with other mutations that, together, conferred high levels of resistance but no consistent cost of resistance. This result may explain why these mutations are so prevalent in clinical quinolone-resistant isolates. In addition, genes involved in cyclic-di-GMP signalling were repeatedly mutated in populations evolved in viscous culture media, suggesting a shared mechanism of adaptation to this CF-like growth environment. Experimental evolutionary approaches to understanding pathogen adaptation should provide an important complement to studies of the evolution of clinical isolates.
authors.affiliation: Department of Biology, Carleton University, Ottawa, Canada. Alex_Wong@carleton.ca
authors.forename: Alex
authors.initials: A
authors.lastname: Wong
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodrigue
authors.forename: Rees
authors.initials: R
authors.lastname: Kassen
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D018929:Cell Culture Techniques; D002939:Ciprofloxacin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics / Q000382:microbiology; D027081:DNA Gyrase / Q000235:genetics*; D019020:Directed Molecular Evolution; D004352:Drug Resistance, Microbial / Q000187:drug effects / Q000235:genetics; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D009154:Mutation; D009894:Opportunistic Infections / Q000235:genetics / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity
chemical_list: D002939:Ciprofloxacin; D027081:DNA Gyrase