Journal article
Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
- Abstract:
- It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.2MB, Terms of use)
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(Preview, Supplementary materials, pdf, 38.3KB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-021-22814-9
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 12
- Article number:
- 2460
- Publication date:
- 2021-04-28
- Acceptance date:
- 2021-03-31
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Keywords:
- Pubs id:
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1169817
- Local pid:
-
pubs:1169817
- Deposit date:
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2021-03-31
- ARK identifier:
Terms of use
- Copyright holder:
- Wheatley et al.
- Copyright date:
- 2021
- Rights statement:
- Copyright © 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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