PUBLICATION
Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular Pathogens by Affecting Both Host and Microbe
- Authors
- Zheng, Q., Wang, Q., Wang, S., Wu, J., Gao, Q., Liu, W.
- ID
- ZDB-PUB-170214-143
- Date
- 2015
- Source
- Chemistry & Biology 22: 1002-7 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/chemical synthesis
- Anti-Bacterial Agents/pharmacology*
- Autophagy/drug effects
- Endoplasmic Reticulum Stress/drug effects
- Mice
- Microbial Sensitivity Tests
- Mycobacterium Infections, Nontuberculous/drug therapy
- Mycobacterium marinum/drug effects*
- Quinolines/chemistry
- Quinolines/pharmacology
- RAW 264.7 Cells
- Stress, Physiological/drug effects
- Thiostrepton/chemical synthesis
- Thiostrepton/pharmacology*
- Zebrafish
- PubMed
- 26211364 Full text @ Chem. Biol.
Citation
Zheng, Q., Wang, Q., Wang, S., Wu, J., Gao, Q., Liu, W. (2015) Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular Pathogens by Affecting Both Host and Microbe. Chemistry & Biology. 22:1002-7.
Abstract
Thiostrepton (TSR) is an archetypal thiopeptide antibiotic possessing a quinaldic acid (QA) moiety in the side ring system. According to the mechanism of TSR previously known to target bacterial ribosome, we recently designed and biosynthesized several TSR derivatives that varied in QA substitution. Utilizing these thiopeptide antibiotics to treat the intracellular pathogen Mycobacterium marinum, we herein report a novel mode of action of TSRs, which induce ER stress-mediated autophagy to enhance host cell defense. This intracellular response, which is sensitive to the modification of the QA group, serves as an indirect but unignorable mechanism for eliminating intracellular pathogens. TSRs are thus the only type of antibiotics, to our knowledge, with the dual action on both the parasitic bacteria and the infected host cells. The newly observed mechanism of TSRs may inspire the future change in the treatment of intracellular pathogens, by taking host response into account.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping