A carregar...
Publicação
Multidrug-resistant bacteria compensate for the epistasis between resistances
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| artigo principal | 2.75 MB | Adobe PDF | ||
| material suplementar 1 | 53.35 KB | Adobe PDF | ||
| material suplementar 2 | 46.26 KB | Microsoft Excel XML | ||
| material suplementar 3 | 30.48 KB | Adobe PDF | ||
| material suplementar 4 | 35.43 KB | Microsoft Excel XML |
Orientador(es)
Resumo(s)
Mutations conferring resistance to antibiotics are typically costly in the absence of the drug, but bacteria can reduce this cost by acquiring compensatory mutations. Thus, the rate of acquisition of compensatory mutations and their effects are key for the maintenance and dissemination of antibiotic resistances. While compensation for single resistances has been extensively studied, compensatory evolution of multiresistant bacteria remains unexplored. Importantly, since resistance mutations often interact epistatically, compensation of multiresistant bacteria may significantly differ from that of single-resistant strains. We used experimental evolution, next-generation sequencing, in silico simulations, and genome editing to compare the compensatory process of a streptomycin and rifampicin double-resistant Escherichia coli with those of single-resistant clones. We demonstrate that low-fitness double-resistant bacteria compensate faster than single-resistant strains due to the acquisition of compensatory mutations with larger effects. Strikingly, we identified mutations that only compensate for double resistance, being neutral or deleterious in sensitive or single-resistant backgrounds. Moreover, we show that their beneficial effects strongly decrease or disappear in conditions where the epistatic interaction between resistance alleles is absent, demonstrating that these mutations compensate for the epistasis. In summary, our data indicate that epistatic interactions between antibiotic resistances, leading to large fitness costs, possibly open alternative paths for rapid compensatory evolution, thereby potentially stabilizing costly multiple resistances in bacterial populations.
Descrição
Palavras-chave
Antibiotic resistance Microbial mutation Cloning Epistasis Mutation Antibiotics Streptomycin Bacterial evolution
Contexto Educativo
Citação
Moura de Sousa J, Balbontı ́ n R, Dur ã o P, Gordo I (2017) Multidru g-resistant bacteria compensate for the epistasis between resistance s. PLoS Biol 15(4): e2001741. https://do i.org/ 10.1371/ journal.pbio.2001 741
Editora
Public Library of Science