Zhang Yuanyuan, Zhang Bin, Han Yunjiao, Zhao Baohua, Wang Shijie
Hebei Normal University, Hebei, 050010, China.
China Shijiazhuang Junlebao Dairy Co. Ltd, Hebei, 050221, China.
BMC Microbiol. 2025 May 26;25(1):324. doi: 10.1186/s12866-025-04040-1.
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.
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.
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.
阪崎肠杆菌可通过食用受污染的乳基食品导致早产儿和新生儿严重感染。然而，序列型4（ST4）阪崎肠杆菌的发病机制仍有待充分阐明。
在本研究中，通过比较毒性、基因组和转录组分析对四株ST4阪崎肠杆菌菌株进行了研究，以阐明其致病特征和机制。多位点序列分型（MLST）表明，在从乳基婴儿和幼儿食品中分离出的36株阪崎肠杆菌属菌株中，ST4阪崎肠杆菌很常见，并且还检测到了13种新的序列型。与其他序列型分离株相比，ST4阪崎肠杆菌表现出更高的肠重与胴体重比（GW/CW）、更强的侵袭和移位能力，以及在人脑微血管内皮细胞（HBMECs）和人U251胶质瘤细胞（U251）中肿瘤坏死因子-α、白细胞介素-1和乳酸脱氢酶（LDH）分泌增加。此外，具有较高GW/CW比的ST4阪崎肠杆菌菌株显著破坏常规血液指标，促进炎症因子分泌，并在乳鼠的肝脏、大脑、脾脏、肾脏和肠道中诱导严重的组织病理学变化。尽管在这些具有不同致病表型的ST4阪崎肠杆菌菌株之间观察到基因组组成和已知毒力因子的差异，但比较转录组分析表明，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内的众多毒力因子和途径的表达，对ST4阪崎肠杆菌的高致病性有很大贡献。
我们的研究结果表明，食源性ST4阪崎肠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。
