Rational design of antibiotic treatment plans: a treatment strategy for managing evolution and reversing resistance.

ABSTRACT: The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to overcoming this challenge. Here we present a data-driven mathematical approach for developing antibiotic treatment plans that can reverse the evolution of antibiotic resistance determinants. We have generated adaptive landscapes for 16 genotypes of the TEM β-lactamase that vary from the wild type genotype "TEM-1" through all combinations of four amino acid substitutions. We determined the growth rate of each genotype when treated with each of 15 β-lactam antibiotics. By using growth rates as a measure of fitness, we computed the probability of each amino

SUBMITTER: Mira PM 

PROVIDER: S-EPMC4422678 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature