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Proteomic Analysis of FNR-Regulated Anaerobiosis in Salmonella Typhimurium

  • Zhen Wang
  • Jingjing Sun
  • Mengdan Tian
  • Zeling Xu
  • Yanhua Liu
  • Jiaqi Fu
  • Aixin YanEmail author
  • Xiaoyun LiuEmail author
Focus: Ion Mobility Spectrometry (IMS): Research Article

Abstract

Bacterial pathogens such as Salmonella enterica serovar Typhimurium (S. Typhimurium) have to cope with fluctuating oxygen levels during infection within host gastrointestinal tracts. The global transcription factor FNR (fumarate nitrate reduction) plays a vital role in the adaptation of enteric bacteria to the low oxygen environment. Nevertheless, a comprehensive profile of the FNR regulon on the proteome level is still lacking in S. Typhimurium. Herein, we quantitatively profiled S. Typhimurium proteome of an fnr-deletion mutant during anaerobiosis in comparison to its parental strain. Notably, we found that FNR represses the expression of virulence genes of Salmonella pathogenicity island 1 (SPI-1) and negatively regulates propanediol utilization by directly binding to the promoter region of the pdu operon. Importantly, we provided evidence that S. Typhimurium lacking fnr exhibited increased antibiotics susceptibility and membrane permeability as well. Furthermore, genetic deletion of fnr leads to decreased bacterial survival in a Caenorhabditis elegans infection model, highlighting an important role of this regulator in mediating host-pathogen interactions.

Keywords

Salmonella Typhimurium The FNR regulon Anaerobiosis Quantitative proteomics 

Notes

Acknowledgements

We thank the members of the Liu and Yan laboratories for the critical reading of this manuscript. This work was financially supported by grants from the National Natural Science Foundation of China (21475005 and 21622501), Clinical Medicine Plus X-Young Scholars Project of Peking University, and the Thousand Young Talents Program to XL, and the Hong Kong University Research Council General Research Fund (17127918) and Shenzhen City Knowledge Innovation Plan (JCYJ20160530174441706) to AY.

Supplementary material

13361_2019_2145_MOESM1_ESM.xlsx (10 kb)
ESM 1 (XLSX 9 kb)
13361_2019_2145_MOESM2_ESM.xlsx (549 kb)
ESM 2 (XLSX 549 kb)
13361_2019_2145_MOESM3_ESM.pdf (107 kb)
Figure S1 A protein volcano plot with the logarithmic values of the abundance ratios on the x-axis. The y-axis plots negative logarithmic p values from three biological replicates. Red and green dots represent upregulated and downregulated proteins respectively with the criterion of two-fold changes and p < 0.05. (PDF 106 kb)
13361_2019_2145_MOESM4_ESM.pdf (245 kb)
Figure S2 The multi scatter plots show the comparison of protein intensities in different biological replicates. The Pearson correlation coefficients were shown in each plot. (PDF 244 kb)
13361_2019_2145_MOESM5_ESM.pdf (184 kb)
Figure S3 Immunoblotting analyses of S. Typhimurium SopB, HilA, PrgH, PduJ and PduT in various genetic backgrounds (WT, Δfnr, ΔarcA) under anaerobic conditions. Full blot images were shown in the top and Coomassie-stained images of corresponding PVDF membranes were shown in the bottom. (PDF 184 kb)

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Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular EngineeringPeking UniversityBeijingChina
  2. 2.School of Biological SciencesThe University of Hong KongHong Kong SARChina
  3. 3.Department of Microbiology, School of Basic Medical SciencesPeking University Health Science CenterBeijingChina

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