genomics of adaptation during experimental evolution of the opportunistic pathogen pseudomonas aeruginosa实验期间适应进化的基因组学的机会病原体铜绿假单胞菌.pdfVIP

Genomics of Adaptation during Experimental Evolution of the Opportunistic Pathogen Pseudomonas aeruginosa Alex Wong1,2*, Nicolas Rodrigue2,3, Rees Kassen2 1 Department of Biology, Carleton University, Ottawa, Canada, 2 Department of Biology, University of Ottawa, Ottawa, Canada, 3 Eastern Cereal and Oilseed Research Centre, Agriculture and Agri-Food Canada, Ottawa, Canada 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 th