RT Journal Article
SR Electronic
T1 High potency of sequential therapy with only β-lactam antibiotics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.20.453050
DO 10.1101/2021.07.20.453050
A1 Aditi Batra
A1 Roderich Roemhild
A1 Emilie Rousseau
A1 Soeren Franzenburg
A1 Stefan Niemann
A1 Hinrich Schulenburg
YR 2021
UL http://biorxiv.org/content/early/2021/07/22/2021.07.20.453050.abstract
AB Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution- informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross- resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.Competing Interest StatementThe authors have declared no competing interest.