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Evolution of high-level resistance during low-level antibiotic exposure.


ABSTRACT: It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are found, whereas at sub-MIC selection resistance is generated by several small-effect resistance mutations that combined confer high-level resistance via three different mechanisms: (i) alteration of the ribosomal RNA target (gidB mutations), (ii) reduction in aminoglycoside uptake (cyoB, nuoG, and trkH mutations), and (iii) induction of the aminoglycoside-modifying enzyme AadA (znuA mutations). These results demonstrate how the strength of the selective pressure influences evolutionary trajectories and that even weak selective pressures can cause evolution of high-level resistance.

SUBMITTER: Wistrand-Yuen E 

PROVIDER: S-EPMC5913237 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Evolution of high-level resistance during low-level antibiotic exposure.

Wistrand-Yuen Erik E   Knopp Michael M   Hjort Karin K   Koskiniemi Sanna S   Berg Otto G OG   Andersson Dan I DI  

Nature communications 20180423 1


It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are fo  ...[more]

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