Recombinant Lactococcus lactis secreting FliC protein nanobodies for resistance against Salmonella enteritidis invasion in the intestinal tract.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Nanobiotechnology Pub Date : 2024-10-16 DOI:10.1186/s12951-024-02904-8
Ming Yang, Kui Gu, Qiang Xu, Renqiao Wen, Jinpeng Li, Changyu Zhou, Yu Zhao, Miwan Shi, Yuan Weng, Boyan Guo, Changwei Lei, Yong Sun, Hongning Wang
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Abstract

Salmonella Enteritidis is a major foodborne pathogen throughout the world and the increase in antibiotic resistance of Salmonella poses a significant threat to public safety. Natural nanobodies exhibit high affinity, thermal stability, ease of production, and notably higher diversity, making them widely applicable for the treatment of viral and bacterial infections. Recombinant expression using Lactococcus lactis leverages both acid resistance and mucosal colonization properties of these bacteria, allowing the effective expression of exogenous proteins for therapeutic effects. In this study, nine specific nanobodies against the flagellar protein FliC were identified and expressed. In vitro experiments demonstrated that FliC-Nb-76 effectively inhibited the motility of S. Enteritidis and inhibited its adhesion to and invasion of HIEC-6, RAW264.7, and chicken intestinal epithelial cells. Additionally, a recombinant L. lactis strain secreting the nanobody, L. lactis-Nb76, was obtained. Animal experiments confirmed that it could significantly reduce the mortality rates of chickens infected with S. Enteritidis, together with alleviating the inflammatory response caused by the pathogen. These results provide a novel strategy for the treatment of antibiotic-resistant S. Enteritidis infection in the intestinal tract.

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重组乳球菌分泌 FliC 蛋白纳米抗体,抵御肠道沙门氏菌入侵。
肠炎沙门氏菌是全球主要的食源性病原体,沙门氏菌抗生素耐药性的增加对公共安全构成了重大威胁。天然纳米抗体具有高亲和性、热稳定性、易生产性和显著的高多样性,因此可广泛用于治疗病毒和细菌感染。利用乳酸乳球菌进行重组表达,可充分利用这些细菌的耐酸性和粘膜定植特性,从而有效表达外源蛋白质,达到治疗效果。本研究鉴定并表达了九种针对鞭毛蛋白 FliC 的特异性纳米抗体。体外实验表明,FliC-Nb-76 能有效抑制肠炎双球菌的运动,并抑制其粘附和侵入 HIEC-6、RAW264.7 和鸡肠道上皮细胞。此外,还获得了能分泌纳米抗体的重组乳杆菌菌株 L. lactis-Nb76。动物实验证实,它能显著降低感染肠炎双球菌的鸡的死亡率,同时减轻病原体引起的炎症反应。这些结果为治疗肠道中的抗生素耐药肠炎球菌感染提供了一种新策略。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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