Yuanyuan Zhang, Bin Zhang, Yunjiao Han, Baohua Zhao, Shijie Wang
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引用次数: 0
Abstract
Background: Cronobacter sakazakii can cause severe infections in premature infants and neonates through the consumption of contaminated milk-based foods. However, the pathogenesis of sequence type 4 (ST4) C. sakazakii remains to be fully elucidated.
Results: In this study, four ST4 C. sakazakii strains were investigated via comparative toxicity, genomic, and transcriptomic analyses to elucidate their pathogenic characteristics and mechanisms. Multilocus sequence typing (MLST) indicated that ST4 C. sakazakii was frequently identified among 36 Cronobacter spp. isolates recovered from milk-based infant and baby foods, and 13 novel STs were also detected. Compared with other ST isolates, ST4 C. sakazakii displayed a higher gut weight to carcass weight ratio (GW/CW), stronger abilities to invade and translocate, and increased secretion of TNF-α, IL-1, and lactate dehydrogenase (LDH) in human brain microvascular endothelial cells (HBMECs) and human U251 glioma cells (U251). Moreover, ST4 C. sakazakii strains with a higher GW/CW ratio significantly disrupted routine blood indices, promoted the secretion of inflammatory factors, and induced severe histopathological changes in the liver, brain, spleen, kidney, and intestine of suckling mice. Although differences in genome composition and known virulence factors were observed among these ST4 C. sakazakii strains with varying pathogenic phenotypes, comparative transcriptomic analyses revealed that the expression of numerous virulence factors and pathways, including ompA, ompW, luxS, rpoS, the Sec secretion system, lipopolysaccharide biosynthesis and assembly, and flagellar assembly, greatly contributed to the high pathogenicity of ST4 C. sakazakii.
Conclusion: Our findings suggest that foodborne ST4 C. sakazakii isolates represent a significant potential threat to food safety and public health, particularly for premature and immunocompromised infants.
背景：阪崎克罗诺杆菌可通过食用受污染的乳基食品引起早产儿和新生儿的严重感染。然而，序列4型（ST4） C. sakazakii的发病机制仍未完全阐明。结果：本研究通过比较毒性、基因组学和转录组学分析对4株ST4阪崎c进行了研究，以阐明其致病特性和机制。多位点序列分型（Multilocus sequence typing， MLST）结果显示，从婴幼儿乳基食品中分离的36株克罗诺杆菌中检出ST4阪崎氏菌，并检出13株新型STs。与其他ST菌株相比，ST4 C. sakazakii菌株在人脑微血管内皮细胞（HBMECs）和人脑胶质瘤细胞（U251）中表现出更高的肠重/体重比（GW/CW），更强的侵袭和转运能力，以及更高的TNF-α、IL-1和乳酸脱氢酶（LDH）的分泌。此外，较高GW/CW比的ST4阪崎c菌显著破坏了哺乳小鼠的血常规指标，促进了炎症因子的分泌，并引起了肝脏、大脑、脾脏、肾脏和肠道的严重组织病理学改变。虽然这些致病表型不同的ST4 C. sakazaki菌株在基因组组成和已知毒力因子方面存在差异，但转录组学比较分析显示，许多毒力因子和途径的表达，包括ompA、ompW、luxS、rpoS、Sec分泌系统、脂多糖生物合成和组装以及鞭毛组装，在很大程度上促成了ST4 C. sakazaki的高致病性。结论：我们的研究结果表明，食源性ST4阪崎胞杆菌分离株对食品安全和公众健康构成重大潜在威胁，特别是对早产儿和免疫功能低下的婴儿。
期刊介绍：
BMC Microbiology is an open access, peer-reviewed journal that considers articles on analytical and functional studies of prokaryotic and eukaryotic microorganisms, viruses and small parasites, as well as host and therapeutic responses to them and their interaction with the environment.
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