@article{Schrader:2021:10.1126/sciadv.abh2037,
author = {Schrader, S and Botella, H and Jansen, R and Ehrt, S and Rhee, K and Nathan, C and Vaubourgeix, J},
doi = {10.1126/sciadv.abh2037},
journal = {Science Advances},
pages = {1--17},
title = {Multiform antimicrobial resistance from a metabolic mutation},
url = {http://dx.doi.org/10.1126/sciadv.abh2037},
volume = {7},
year = {2021}
}
TY - JOUR
AB - A critical challenge for microbiology and medicine is how to cure infections by bacteria that survive antibiotic treatment by persistence or tolerance. Seeking mechanisms behind such high survival, we developed a forward-genetic method for efficient isolation of high24 survival mutants in any culturable bacterial species. We found that perturbation of an essential biosynthetic pathway (arginine biosynthesis) in a mycobacterium generated three distinct forms of resistance to diverse antibiotics, each mediated by induction of WhiB7— high persistence and tolerance to kanamycin, high survival upon exposure to rifampicin, and MIC-shifted resistance to clarithromycin. As little as one base change in a gene encoding a metabolic pathway component conferred multiple forms of resistance to multiple antibiotics with different targets. This extraordinary resilience may help explain how sub31 sterilizing exposure to one antibiotic in a regimen can induce resistance to others and invites development of drugs targeting the mediator of multiform resistance, WhiB7.
AU - Schrader,S
AU - Botella,H
AU - Jansen,R
AU - Ehrt,S
AU - Rhee,K
AU - Nathan,C
AU - Vaubourgeix,J
DO - 10.1126/sciadv.abh2037
EP - 17
PY - 2021///
SN - 2375-2548
SP - 1
TI - Multiform antimicrobial resistance from a metabolic mutation
T2 - Science Advances
UR - http://dx.doi.org/10.1126/sciadv.abh2037
UR - https://www.science.org/doi/10.1126/sciadv.abh2037
UR - http://hdl.handle.net/10044/1/90679
VL - 7
ER -