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Elife DOI:10.7554/eLife.20420

Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.

Publication TypeJournal Article
Year of Publication2017
AuthorsGomez, JE, Kaufmann-Malaga, BB, Wivagg, CN, Kim, PB, Silvis, MR, Renedo, N, Ioerger, TR, Ahmad, R, Livny, J, Fishbein, S, Sacchettini, JC, Carr, SA, Hung, DT
JournalElife
Volume6
Date Published2017 Feb 21
ISSN2050-084X
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.

DOI10.7554/eLife.20420
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28220755?dopt=Abstract

Alternate JournalElife
PubMed ID28220755
PubMed Central IDPMC5319836