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Antibiotic Dereplication Using the Antibiotic Resistance Platform
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Predictable Phenotypes of Antibiotic Resistance Mutations.

M Knopp1, D I Andersson2

  • 1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

Mbio
|May 17, 2018
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Summary
This summary is machine-generated.

Antibiotic resistance mutations

Keywords:
Escherichia coliSalmonellaStrain specificityantibiotic resistanceepistasisfitness

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genetics

Background:

  • Antibiotic-resistant bacteria pose a significant global health threat.
  • Predicting the evolutionary trajectory of resistance mutations is crucial for effective treatment strategies.
  • Epistatic interactions between resistance mutations may complicate predictions of their stability.

Purpose of the Study:

  • To investigate epistatic interactions between chromosomal antibiotic resistance mutations.
  • To determine how strain background and genetic distance influence resistance and fitness phenotypes.
  • To assess the predictability of combined resistance mutation effects.

Main Methods:

  • Analysis of 13 chromosomal resistance mutations across 10 host strains of *Salmonella enterica* and *Escherichia coli*.
  • Systematic screening for epistatic interactions between multiple resistance mutations.
  • Evaluation of strain-independent phenotypes for various resistance mutations.

Main Results:

  • Epistatic interactions between antibiotic resistance mutations were found to be rare.
  • The combined effects of multiple resistance mutations on resistance and fitness were largely predictable.
  • Most resistance mutations, particularly target alteration mutations, exhibited strain-independent phenotypes across species.
  • A few outlier mutations demonstrated significant strain-specific effects.

Conclusions:

  • Antibiotic resistance mutation interactions are generally predictable, simplifying evolutionary forecasting.
  • Strain background has a limited but sometimes critical impact on resistance mutation phenotypes.
  • Understanding these predictable interactions aids in combating the spread of antibiotic resistance.