Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China.
Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Microb Pathog. 2019 Nov;136:103701. doi: 10.1016/j.micpath.2019.103701. Epub 2019 Aug 28.
The objective of this study was to comprehensively identify the target genes induced by acid stimulation in Salmonella, and to clarify the relativity of acid tolerance and antimicrobial peptide resistance. A clinical S. Typhimurium strain, S6, was selected and performed a transcriptome analysis under the acid tolerance response. In total, we found 1461 genes to be differentially expressed, including 721 up-regulated and 740 down-regulated genes. Functional annotation revealed differentially expressed genes to be associated with regulation, metabolism, transport, virulence, and motility. Interestingly, KEGG pathway analysis demonstrated that the induced genes by acid were enriched in cationic antimicrobial peptide resistance, sulfur relay system, ABC transporters, and two-component system pathway. Therein, PhoQ belonging to the two-component system PhoP-PhoQ that promotes virulence by detecting the macrophage phagosome and controls the transcript levels of many genes associated with the resistance to AMPs; MarA, a multiple antibiotic resistance factor; SapA, one of the encoding gene of sapABCDF operon that confers resistance to small cationic peptides of Salmonella; YejB, one of the encoding gene of yejABEF operon that confers resistance to antimicrobial peptides and contributes to the virulence of Salmonella, were all induced by acid stimulation, and could potentially explain that there is a correlation between acid tolerance and AMPs resistance, and finally affects the virulence of intracellular pathogenic bacteria.
本研究旨在全面鉴定酸刺激诱导的沙门氏菌靶基因，并阐明酸耐受与抗抗菌肽耐药的相关性。选择一株临床分离的鼠伤寒沙门氏菌 S6 株，在耐酸应答条件下进行转录组分析。共发现 1461 个差异表达基因，其中 721 个上调，740 个下调。功能注释显示差异表达基因与调控、代谢、转运、毒力和运动性有关。有趣的是，KEGG 通路分析表明，酸诱导的基因富集在阳离子抗菌肽耐药、硫代传递系统、ABC 转运体和双组分系统途径中。其中，属于双组分系统 PhoP-PhoQ 的 PhoQ 通过检测巨噬细胞吞噬体促进毒力，控制与 AMPs 耐药相关的许多基因的转录水平；MarA 是多种抗生素耐药因子；SapA 是编码 sapABCDF 操纵子的基因之一，赋予沙门氏菌对小阳离子肽的耐药性；YejB 是编码 yejABEF 操纵子的基因之一，赋予抗菌肽耐药性，并有助于沙门氏菌的毒力，均受酸刺激诱导，这可能解释了酸耐受与 AMPs 耐药之间存在相关性，并最终影响细胞内致病菌的毒力。
