Emerson Lisa E, Bhimani Saloni, Rainey Andrew L, Maurelli Anthony T, Ferraro Mariola J
Microbiology and Cell Science Department, IFAS, University of Florida, Gainesville, Florida, USA.
Clinical and Translational Science Institute, University of Florida, Gainesville, Florida, USA.
Infect Immun. 2025 Feb 18;93(2):e0048524. doi: 10.1128/iai.00485-24. Epub 2025 Jan 13.
infections pose significant public health challenges worldwide. The diversity of strains, particularly those isolated from environmental and clinical sources, necessitates innovative approaches to prevention and treatment. Previous research has shown that small extracellular vesicles (sEVs) produced by macrophages during Typhimurium infection can induce robust immune responses when used as a vaccine, offering complete protection in systemic infection models. In this study, we isolated 120 strains from qPCR -positive wastewater samples collected in Gainesville, FL. These strains underwent enrichment, selection, and biochemical confirmation, followed by serotyping and whole genome sequencing. Two isolates, subsp. diarizonae (Diarizonae) and serovar Enteritidis, were selected for further analysis based on community prevalence and clinical severity. We also assessed the ability of sEVs produced by . Typhimurium-infected macrophages to induce immune responses against these heterologous and circulating strains in mice. Immunization with sEVs induced robust antigen-specific SIgA and IgG responses against . Typhimurium, Enteritidis, and Diarizonae, with high titers observed in sera and fecal samples. Proteomic analysis revealed differential expression of proteins in these strains, including antigenic proteins present in sEVs such as OmpA, FliC, or OmpD. Moreover, this study highlights the role of wastewater-based epidemiology (WBE) as a tool for environmental surveillance, offering a complementary perspective on dynamics within a population. Integrating WBE with traditional surveillance methods, along with the promising results of sEV-based vaccination, provides a pragmatic strategy for developing effective preventative measures against infections, addressing the diversity of non-typhoidal strains.
感染在全球范围内构成了重大的公共卫生挑战。菌株的多样性，尤其是那些从环境和临床来源分离出的菌株，使得预防和治疗需要创新方法。先前的研究表明，鼠伤寒感染期间巨噬细胞产生的小细胞外囊泡（sEVs）用作疫苗时可诱导强烈的免疫反应，在全身感染模型中提供完全保护。在本研究中，我们从佛罗里达州盖恩斯维尔收集的qPCR阳性废水样本中分离出120株菌株。这些菌株经过富集、筛选和生化鉴定，随后进行血清分型和全基因组测序。基于群落流行率和临床严重程度，选择了两个分离株，即亚利桑那亚种（Diarizonae）和肠炎血清型，进行进一步分析。我们还评估了鼠伤寒感染的巨噬细胞产生的sEVs在小鼠中诱导针对这些异源和流行菌株的免疫反应的能力。用sEVs免疫诱导了针对鼠伤寒、肠炎和亚利桑那的强烈抗原特异性SIgA和IgG反应，在血清和粪便样本中观察到高滴度。蛋白质组学分析揭示了这些菌株中蛋白质的差异表达，包括sEVs中存在的抗原蛋白，如OmpA、FliC或OmpD。此外，本研究强调了基于废水的流行病学（WBE）作为环境监测工具的作用，为人群内的动力学提供了补充观点。将WBE与传统监测方法相结合，以及基于sEV的疫苗接种的有前景的结果，为制定针对感染的有效预防措施提供了务实策略，应对非伤寒菌株的多样性。
