In vivo evolution of antibiotic resistance in vancomycin-resistant Enterococcus
Microbial Ecology and Applied Microbiology
Final Report Abstract
The evolution of antibiotic resistance is one of the major threats of our time. There is a significant gap between the evolutionary process undertaken by bacteria when exposed to antibiotics, and how physicians can use, interpret, and exploit such information to increase clinical decision making. Improving our capacity to predict when and how antibiotic resistance will evolve can have an impactful effect on how we approach the balancing act of curtailing disease progression while minimizing the risk of resistance evolution. To this end I have systematically evaluated the potential of experimental evolution to test the repeatability of the evolutionary process that take place within a patient. I used a simplified and tractable system in the laboratory, taking advantage of an extensive repository of blood isolates of Enterococcus faecium where patterns of the evolution of antibiotic resistance was seen in vivo. I used experimental evolution to “re-play” the evolutionary tape to examine whether the same adaptive pathways selected in vivo can be recaptured in vitro. From these experiments I learned that while laboratory evolved lineages reach similar or higher levels of resistance as those seen within patients, the magnitude of gains in resistance are strongly dependent on the specific starting genotype. Similarly, the capacity to survive the experimental regime was significantly dependent on the starting genotype. Moreover, multiple genetic mechanisms were identified among the different isolates obtained from the different patients, thus suggesting that multiple mechanisms of resistance against daptomycin may be available to E. faecium. Altogether, the findings in this study highlight that evolution of resistance in a clinical context can be intricate but can be predictable at the genotype level. This is important because it indicates that not all bacterial infections can be treated the same, and that the likelihood of resistance evolution can be associated to the genotype causing the disease. It remains to be seen whether the same genetic pathways can be recaptured under laboratory conditions and to what extent the evolution of resistance against one drug includes changes in resistance against other antibiotics.
Publications
- (2020) Variants in ampD and dacB lead to in vivo resistance evolution of Pseudomonas aeruginosa within the central nervous system. J Antimicrob Chemother. 75: 3405-3408
Barbosa C, Gregg KS, Woods RJ
(See online at https://doi.org/10.1093/jac/dkaa324) - (2020) Why is preventing antibiotic resistance so hard? Analysis of failed resistance management. Evol Med Public Health 2020: 102–108
Zhou S, Barbosa C, Woods RJ
(See online at https://doi.org/10.1093/emph/eoaa020)
