Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China.
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.
Res Microbiol. 2022 Jan-Feb;173(1-2):103886. doi: 10.1016/j.resmic.2021.103886. Epub 2021 Oct 26.
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, acrB gene deletion strain CR, and double gene deletion strain CR 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/CR, CR/CR and CR/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.
贝氏（BaeSR）双组分系统和 AcrB 外排泵与沙门氏菌对抗生素的耐药性密切相关。然而，双组分系统、外排泵与沙门氏菌蛋白磷酸化之间的关系尚未得到充分的理解。在本研究中，使用了鼠伤寒沙门氏菌环丙沙星耐药株 CR、baeSR 基因缺失株 CR、acrB 基因缺失株 CR 和双基因缺失株 CR，基于无标记、定量磷酸化修饰蛋白质组学技术，来探索具有显著差异的磷酸化蛋白。结果，在这四种菌株中鉴定出了 213 种磷酸化蛋白中的 363 个磷酸化位点。70%以上的磷酸化位点为丝氨酸磷酸化。在 CR/CR、CR/CR 和 CR/CR 比较组中，分别有 36、37 和 49 个磷酸化位点发生了显著改变。生物信息学分析表明，这些差异磷酸化蛋白的主要富集途径为代谢途径、抗生素生物合成、磷酸转移酶系统（PTS）、ABC 转运体和脂多糖生物合成。此外，还鉴定出 21 个与抗生素耐药性相关的差异磷酸化蛋白。这些结果表明，BaeSR 双组分系统和 AcrB 外排泵影响鼠伤寒沙门氏菌中蛋白质的磷酸化，可能通过影响蛋白质磷酸化来影响鼠伤寒沙门氏菌的耐药性和毒力，为探索沙门氏菌耐药机制提供了新的思路。
