Batsaikhan Buyandelger, Lin Pei-Chun, Shigemura Katsumi, Wu Yu-Wei, Onishi Reo, Chang Pei-Ru, Cheng Hung-Yen, Fang Shiuh-Bin
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of Emergency Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
J Microbiol Immunol Infect. 2025 Feb;58(1):38-47. doi: 10.1016/j.jmii.2024.09.002. Epub 2024 Sep 19.
Nontyphoidal Salmonella (NTS) outbreaks of invasive diseases are increasing. Whether the genetic diversity of invasive NTS correlates with the clinical characteristics and bacteremia development in NTS infections remains unclear. In this study, we compared the global transcriptomes between bacteremic and nonbacteremic NTS strains after their interaction with human intestinal epithelial cells in vitro.
We selected clinical isolates obtained from stool and blood samples of patients with or without bacteremia and patients with high and low C-reactive protein (CRP) levels. The bacterial RNA samples were isolated after coculturing with Caco-2 cells for RNA sequencing and subsequent analyses.
CRP is an unreliable predictive maker for NTS bacteremia with a median CRP level of 1.6 mg/dL. Certain Salmonella Pathogenicity Island (SPI)-1 genes (sipC, sipA, sicA, sipD, and sipB), SPI-2 genes (ssaP, ssrA, and ssaS), and six SPI-4 genes (siiA, siiB, siiC, siiD, siiE, and siiF) remained upregulated in the bacteremic blood-derived strains but significantly downregulated in the nonbacteremic strains after their interaction with Caco-2 cells. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis identified that arginine biosynthesis, ascorbate and aldarate metabolism, and phosphotransferase system pathways were activated in bacteremic NTS strains after Caco-2 cell priming.
CRP levels were not correlated with bacteremia development. Significant regulation of certain SPI genes in bacteremic NTS strains after Caco-2 cell priming; bacteremia development might be influenced by the host immune response and the extent to which specific metabolism pathways in NTS strains can be prevented from invading the bloodstream.
侵袭性疾病的非伤寒沙门氏菌（NTS）疫情正在增加。侵袭性NTS的遗传多样性是否与NTS感染的临床特征和菌血症发展相关仍不清楚。在本研究中，我们比较了体外与人肠道上皮细胞相互作用后菌血症性和非菌血症性NTS菌株之间的全局转录组。
我们选择了从有或无菌血症的患者以及高和低C反应蛋白（CRP）水平的患者的粪便和血液样本中获得的临床分离株。与Caco-2细胞共培养后分离细菌RNA样本用于RNA测序及后续分析。
CRP是NTS菌血症的不可靠预测指标，CRP中位数水平为1.6mg/dL。某些沙门氏菌致病岛（SPI）-1基因（sipC、sipA、sicA、sipD和sipB）、SPI-2基因（ssaP、ssrA和ssaS）以及六个SPI-4基因（siiA、siiB、siiC、siiD、siiE和siiF）在与Caco-2细胞相互作用后，在菌血症性血液来源菌株中仍上调，但在非菌血症菌株中显著下调。京都基因与基因组百科全书（KEGG）通路分析表明，在Caco-2细胞启动后，菌血症性NTS菌株中的精氨酸生物合成、抗坏血酸和醛糖代谢以及磷酸转移酶系统通路被激活。
CRP水平与菌血症发展无关。Caco-2细胞启动后，菌血症性NTS菌株中某些SPI基因有显著调控；菌血症发展可能受宿主免疫反应以及NTS菌株中特定代谢通路被阻止侵入血流的程度影响。
