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Adaptive Processes Change as Multiple Functions Evolve.

Portia M Mira1, Bjørn Østman1, Candace Guzman-Cole2

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This summary is machine-generated.

Epistasis impacts bacterial antibiotic resistance evolution. The blaTEM-50 variant showed more epistatic interactions than blaTEM-85, suggesting additive interactions better optimize resistance phenotypes.

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genetics

Background:

  • Epistasis, the interaction between gene mutations, influences bacterial adaptation to antibiotics.
  • The blaTEM gene variants, blaTEM-50 and blaTEM-85, confer different levels of resistance to cephalosporins and beta-lactamase inhibitors.
  • Understanding these differences is crucial for predicting bacterial evolution under antibiotic pressure.

Purpose of the Study:

  • To compare the evolutionary landscapes and epistatic interactions of blaTEM-50 and blaTEM-85.
  • To investigate how substitutions within these variants affect bacterial fitness and antibiotic resistance.
  • To determine the role of epistasis versus additive interactions in the evolution of antibiotic resistance.

Main Methods:

  • Comparative analysis of blaTEM-50 and blaTEM-85 evolution.
  • Assessment of epistatic interactions among substitutions within each variant.
  • Measurement of bacterial growth rates across varying antibiotic concentrations.

Main Results:

  • More epistatic interactions were observed in blaTEM-50 compared to blaTEM-85.
  • Additive interactions, particularly in blaTEM-85 precursors, led to increased growth rates with rising antibiotic concentrations.
  • Full cephalosporin resistance for blaTEM-50 requires selection from multiple cephalosporins, while blaTEM-85 evolves faster with a single beta-lactam/inhibitor combination.

Conclusions:

  • Epistatic interactions in blaTEM-50 are more complex than additive interactions in blaTEM-85.
  • Additive interactions appear more effective in optimizing bacterial phenotypes for antibiotic resistance.
  • Exposure to diverse cephalosporins may enhance TEM enzyme's resistance to individual cephalosporins, contrary to initial expectations.