Quantitative phosphoproteomics reveals the effect of baeSR and acrB genes on protein phosphorylation in Salmonella enterica serovar typhimurium

Caili Qi; Feifei Sun; Qiling Wei; Jun Xu; Rui Li; Lin Zhang; Fang Lu; Xidi Jiang; Hengfeng Fu; Chunxiao Zhang; Lin Li

doi:10.1016/j.resmic.2021.103886

Quantitative phosphoproteomics reveals the effect of baeSR and acrB genes on protein phosphorylation in Salmonella enterica serovar typhimurium

Res Microbiol. 2022 Jan-Feb;173(1-2):103886. doi: 10.1016/j.resmic.2021.103886. Epub 2021 Oct 26.

Authors

Caili Qi¹, Feifei Sun², Qiling Wei¹, Jun Xu¹, Rui Li¹, Lin Zhang¹, Fang Lu¹, Xidi Jiang¹, Hengfeng Fu¹, Chunxiao Zhang¹, Lin Li³

Affiliations

¹ Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China.
² Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei, Anhui 230036, PR China.
³ Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei, Anhui 230036, PR China. Electronic address: lilinah@126.com.

PMID: 34715324
DOI: 10.1016/j.resmic.2021.103886

Abstract

The BaeSR two-component system and the AcrB efflux pump are closely associated with Salmonella resistance to antibiotics. However, the relationship between the two-component system, efflux pumps and protein phosphorylation of Salmonella is poorly understood. In this study, Salmonella typhimurium ciprofloxacin-resistant strain CR, baeSR gene deletion strain CR^ΔbaeSR, acrB gene deletion strain CR^ΔacrB, and double gene deletion strain CR^{ΔbaeSRΔacrB} were used to explore phosphorylated proteins with significant difference, based on non-marker, quantitative phosphorylation modified proteomics technique. Consequently, 363 phosphosites of 213 phosphoproteins were identified in the four strains. More than 70% of the phosphosites were serine phosphorylation. In the CR^ΔbaeSR/CR, CR^ΔacrB/CR and CR^{ΔbaeSRΔacrB}/CR comparison groups, 36, 37 and 49 phosphosites were significantly altered, respectively. Bioinformatic analysis revealed that the main enrichment pathways of these differentially phosphorylated proteins were metabolic pathways, biosynthesis of antibiotics, phosphotransferase system (PTS), ABC transporters, and lipopolysaccharide biosynthesis. Furthermore, 21 differentially phosphorylated proteins were identified to be associated with antibiotic resistance. These results suggest that the BaeSR two-component system and the AcrB efflux pump affect the phosphorylation of proteins in S. typhimurium and may influence the drug resistance and virulence of S. typhimurium by affecting protein phosphorylation, providing a new idea to explore the mechanism of drug resistance in Salmonella.

Keywords: Drug resistance; Quantitative phosphoproteomics; S. typhimurium; Virulence; acrB; baeSR.

MeSH terms

Anti-Bacterial Agents / metabolism
Anti-Bacterial Agents / pharmacology
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Drug Resistance, Multiple, Bacterial / genetics
Membrane Transport Proteins / genetics
Microbial Sensitivity Tests
Phosphorylation
Salmonella enterica*
Salmonella typhimurium* / metabolism
Serogroup

Substances

Anti-Bacterial Agents
Bacterial Proteins
Membrane Transport Proteins