PUBLICATION
Optimal translational fidelity is critical for Salmonella virulence and host interactions
- Authors
- Fan, Y., Thompson, L., Lyu, Z., Cameron, T.A., De Lay, N.R., Krachler, A.M., Ling, J.
- ID
- ZDB-PUB-190405-6
- Date
- 2019
- Source
- Nucleic acids research 47(10): 5356-5367 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Bacterial Proteins/metabolism*
- Cell Line
- Down-Regulation
- Gene Expression Regulation, Bacterial*
- Genome, Bacterial
- Genomic Islands*
- Host Microbial Interactions*
- Humans
- Macrophages/metabolism
- Mice
- Protease La/metabolism*
- Salmonella typhimurium/genetics
- Salmonella typhimurium/pathogenicity*
- Sequence Analysis, RNA
- Transcription Factors/metabolism*
- Virulence
- Virulence Factors/genetics
- Zebrafish
- PubMed
- 30941426 Full text @ Nucleic Acids Res.
Citation
Fan, Y., Thompson, L., Lyu, Z., Cameron, T.A., De Lay, N.R., Krachler, A.M., Ling, J. (2019) Optimal translational fidelity is critical for Salmonella virulence and host interactions. Nucleic acids research. 47(10):5356-5367.
Abstract
Translational fidelity is required for accurate flow of genetic information, but is frequently altered by genetic changes and environmental stresses. To date, little is known about how translational fidelity affects the virulence and host interactions of bacterial pathogens. Here we show that surprisingly, either decreasing or increasing translational fidelity impairs the interactions of the enteric pathogen Salmonella Typhimurium with host cells and its fitness in zebrafish. Host interactions are mediated by Salmonella pathogenicity island 1 (SPI-1). Our RNA sequencing and quantitative RT-PCR results demonstrate that SPI-1 genes are among the most down-regulated when translational fidelity is either increased or decreased. Further, this down-regulation of SPI-1 genes depends on the master regulator HilD, and altering translational fidelity destabilizes HilD protein via enhanced degradation by Lon protease. Our work thus reveals that optimal translational fidelity is pivotal for adaptation of Salmonella to the host environment, and provides important mechanistic insights into this process.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping