Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment
Name
Gomez-2017-Ribosomal mutations promote the evo.pdf
Size
4.27 MB
Format
Adobe PDF
Checksum (MD5)
0b5b564a409e26681dc7f18b9abcb1c9
Author(s)
Gomez, James E
Kaufmann-Malaga, Benjamin B
Wivagg, Carl N
Kim, Peter B
Silvis, Melanie R
Renedo, Nikolai
Ioerger, Thomas R
Ahmad, Rushdy
Livny, Jonathan
Fishbein, Skye
Date Issued
February 2017
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Gomez, James E et al. “Ribosomal Mutations Promote the Evolution of Antibiotic Resistance in a Multidrug Environment.” eLife 6 (2017): n. pag.
Version
Final published version
Abstract
Antibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/eLife.20420
