Cuomo Paola, Medaglia Chiara, Casillo Angela, Gentile Antonio, Fruggiero Carmine, Corsaro Maria Michela, Capparelli Rosanna
Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy.
Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy.
Front Immunol. 2024 Dec 11;15:1450600. doi: 10.3389/fimmu.2024.1450600. eCollection 2024.
serovar Rissen ( Rissen) is an emerging causative agent of foodborne diseases. The current emergence of antibiotic resistance makes necessary alternative therapeutic strategies. In this study, we investigated the potential of a phage-resistant strain of Rissen (R) as a tool for developing an effective lipopolysaccharide (LPS)-based vaccine. The LPS O-antigen is known to play critical roles in protective immunity against . However, the high toxicity of the LPS lipid A moiety limits its use in vaccines. Here, we demonstrated that the acquisition of bacteriophage resistance by Rissen leads to structural modifications in the LPS structure. Using NMR and mass spectrometry, we characterized the LPS from phage-resistant strains as a smooth variant bearing under-acylated Lipid A portions (penta- and tetra-acylated forms). We then combined RT-qPCR and NMR-based metabolomics to explore the effects of phage resistance and LPS modification on bacterial fitness and virulence. Finally, we conducted studies to determine whether lysogeny-induced remodeling of LPS affects the host immune response. Results revealed that the under-acylated variant of LPS from attenuates the inflammatory response in BALB/c mice, while eliciting a specific antibody response that protects against Rissen (R) infection. In conclusion, our findings suggest that phage resistance, through lipid A modification, may offer a novel strategy for reducing LPS toxicity, highlighting its potential as a promising biological approach for developing LPS-based vaccines against infections.
里森血清型（Rissen）是一种新出现的食源性疾病病原体。目前抗生素耐药性的出现使得有必要采取替代治疗策略。在本研究中，我们研究了里森噬菌体抗性菌株（R）作为开发基于脂多糖（LPS）的有效疫苗工具的潜力。已知LPS O抗原在针对……的保护性免疫中起关键作用。然而，LPS脂质A部分的高毒性限制了其在疫苗中的应用。在这里，我们证明里森获得噬菌体抗性会导致LPS结构发生改变。利用核磁共振（NMR）和质谱，我们将噬菌体抗性菌株的LPS表征为一种带有酰化不足的脂质A部分（五酰化和四酰化形式）的光滑变体。然后，我们结合逆转录定量聚合酶链反应（RT-qPCR）和基于NMR的代谢组学来探索噬菌体抗性和LPS修饰对细菌适应性和毒力的影响。最后，我们进行了……研究，以确定溶原性诱导的LPS重塑是否会影响宿主免疫反应。结果显示，来自……的LPS酰化不足变体减弱了BALB/c小鼠的炎症反应，同时引发了针对里森（R）感染的特异性抗体反应。总之，我们的研究结果表明，通过脂质A修饰产生的噬菌体抗性可能为降低LPS毒性提供一种新策略，突出了其作为开发针对……感染的基于LPS疫苗的有前景的生物学方法的潜力。
