Eagle Effect in Nonreplicating Persister Mycobacteria

We determined the microbicidal activities of antibacterials against nonreplicating Mycobacterium smegmatis grown in a starvation-based Loebel model for persistence. Whereas most drugs lost their activity, fluoroquinolones retained lethal potency. Dose-response characterizations showed a paradoxical...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Mu-Lu, Tan, Jasmie, Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Mechanisms of Action: Physiological Effects
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649170/
https://www.ncbi.nlm.nih.gov/pubmed/26349831
http://dx.doi.org/10.1128/AAC.01476-15
_version_ 1782401316467769344
author Wu, Mu-Lu
Tan, Jasmie
Dick, Thomas
author_facet Wu, Mu-Lu
Tan, Jasmie
Dick, Thomas
author_sort Wu, Mu-Lu
collection PubMed
description We determined the microbicidal activities of antibacterials against nonreplicating Mycobacterium smegmatis grown in a starvation-based Loebel model for persistence. Whereas most drugs lost their activity, fluoroquinolones retained lethal potency. Dose-response characterizations showed a paradoxical more-drug-kills-less Eagle effect. Pretreatment of cultures with chloramphenicol blocked the lethal action of the gyrase inhibitors. These results suggest that fluoroquinolones at low concentrations trigger a protein synthesis-dependent cell death pathway and shut off this suicide pathway at elevated concentrations.
format Online
Article
Text
id pubmed-4649170
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-46491702015-12-10 Eagle Effect in Nonreplicating Persister Mycobacteria Wu, Mu-Lu Tan, Jasmie Dick, Thomas Antimicrob Agents Chemother Mechanisms of Action: Physiological Effects We determined the microbicidal activities of antibacterials against nonreplicating Mycobacterium smegmatis grown in a starvation-based Loebel model for persistence. Whereas most drugs lost their activity, fluoroquinolones retained lethal potency. Dose-response characterizations showed a paradoxical more-drug-kills-less Eagle effect. Pretreatment of cultures with chloramphenicol blocked the lethal action of the gyrase inhibitors. These results suggest that fluoroquinolones at low concentrations trigger a protein synthesis-dependent cell death pathway and shut off this suicide pathway at elevated concentrations. American Society for Microbiology 2015-11-17 2015-12 /pmc/articles/PMC4649170/ /pubmed/26349831 http://dx.doi.org/10.1128/AAC.01476-15 Text en Copyright © 2015 Wu et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Mechanisms of Action: Physiological Effects
Wu, Mu-Lu
Tan, Jasmie
Dick, Thomas
Eagle Effect in Nonreplicating Persister Mycobacteria
title Eagle Effect in Nonreplicating Persister Mycobacteria
title_full Eagle Effect in Nonreplicating Persister Mycobacteria
title_fullStr Eagle Effect in Nonreplicating Persister Mycobacteria
title_full_unstemmed Eagle Effect in Nonreplicating Persister Mycobacteria
title_short Eagle Effect in Nonreplicating Persister Mycobacteria
title_sort eagle effect in nonreplicating persister mycobacteria
topic Mechanisms of Action: Physiological Effects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649170/
https://www.ncbi.nlm.nih.gov/pubmed/26349831
http://dx.doi.org/10.1128/AAC.01476-15
work_keys_str_mv AT wumulu eagleeffectinnonreplicatingpersistermycobacteria
AT tanjasmie eagleeffectinnonreplicatingpersistermycobacteria
AT dickthomas eagleeffectinnonreplicatingpersistermycobacteria

Ejemplares similares