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.
Highlights
In the mid-1800’s, Louis Pasteur advised microbiologists to think of the human body as a ‘‘culture vessel’’ for microbes, in the context of understanding immunity [1]
We investigate adaptation of the bacterium Pseudomonas aeruginosa to laboratory conditions that resemble the lungs of cystic fibrosis patients and to quinolone antibiotics
Experimental evolution has a rich history in studying basic evolutionary processes (e.g., [11,12,13,14] for reviews), as well as more applied topics such as the evolution of antibiotic resistance [15,16] and of virulence [7]
Summary
In the mid-1800’s, Louis Pasteur advised microbiologists to think of the human body as a ‘‘culture vessel’’ for microbes, in the context of understanding immunity [1]. The last 15 years have seen a number of studies of in vivo genome evolution in select pathogens, primarily viruses (e.g., [7,8]) and bacteria (e.g., [9,10]), that shed vital insight onto the genetic changes that occur during epidemics or chronic infections The importance of these changes for pathogen fitness in a host can be difficult to ascertain, because it is rarely possible to establish with certainty that the observed mutations are adaptive, since some neutral or deleterious mutations may accumulate through drift or by hitchhiking with adaptive mutations. For these reasons we have turned to a complementary approach, laboratory selection experiments, to provide an understanding of the broad patterns and principles of pathogen
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