氨苄西林胁迫下阪崎克罗诺杆菌维持连续休眠态的转录组学分析

Transcriptomic Analysis of Cronobacter sakazakii Maintaining Dormancy Continuum under Ampicillin Stress

摘要:

阪崎克罗诺杆菌是奶粉中常见的食源致病菌，在压力胁迫下会进入连续休眠态。该研究通过转录组测序技术分析氨苄西林压力胁迫下形成的连续休眠态菌的基因表达变化差异，共筛选出220个显著上调基因和416个显著下调基因；并对差异表达基因进行GO和KEGG富集分析。结果表明，与代谢活性、运动能力（鞭毛合成）、细胞分裂相关基因表达整体显著下调；与药物外排泵、细胞形态改变相关的部分基因表达显著上调；GO富集分析结果还提示严谨反应、毒素抗毒素系统（TAS）相关基因表达显著上调，TAS可能通过调控下游mRNA和NAD+促进连续休眠态的形成。因此，在氨苄西林胁迫下严谨反应可能通过级联调节激活TAS表达，从而促进连续休眠态形成。在该状态下，阪崎克罗诺杆菌通过降低代谢活性、减弱运动能力、抑制细胞分裂，同时改变细胞形态，并增强药物外排能力，从而维持连续休眠态。研究结果为防控压力胁迫下产生的连续休眠态阪崎克罗诺杆菌奠定了理论基础。

Abstract:

Cronobacter sakazakii is a common food-borne pathogen in milk powder, which enters the state of dormancy continuum under stress. Transcriptome sequencing was used in the present study to analyze the changes in gene expression in bacteria maintaining dormancy continuum formed under ampicillin stress. A total of 220 and 416 genes were significantly upregulated and downregulated, respectively. Next, GO and KEGG enrichment analyses were performed on differentially expressed genes. Genes related to metabolic activity, motility (flagellar synthesis), and cell division were significantly downregulated in general. Meanwhile, certain genes related to drug efflux pumps and cell morphological changes were significantly upregulated. Similarly, the GO enrichment analysis indicated that genes related to the stringent response and toxin-antitoxin system (TAS) were significantly upregulated. In particular, TAS may promote the formation of dormancy continuum by regulating downstream mRNAs and NAD+. Therefore, stringent response under ampicillin stress may activate TAS expression through cascade regulation, thereby promoting the formation of dormancy continuum. Under stress, C. sakazakii maintains dormancy continuum by reducing metabolic activity, weakening motility, inhibiting cell division, changing cell morphology, and enhancing drug efflux. These findings lay a theoretical foundation for the prevention and control of the dormancy continuum of C. sakazakii under stress.