Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
PLoS Negl Trop Dis. 2013 Aug 1;7(8):e2335. doi: 10.1371/journal.pntd.0002335. Print 2013.
Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.
METHODOLOGY/PRINCIPAL FINDINGS: To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.
CONCLUSIONS/SIGNIFICANCE: Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers.
伤寒沙门氏菌血清型 Typhi 可在感染个体的胆道中定植并持续存在，导致无症状慢性携带状态。慢性携带者可能成为社区内持续感染的潜在储主，并可能将感染引入易感个体和新社区。人们对宿主和病原体在慢性携带者胆道中的相互作用知之甚少，目前也没有可靠的诊断检测方法来识别无症状伤寒沙门氏菌携带。
方法/主要发现：为了研究携带伤寒沙门氏菌期间胆道中的宿主-病原体相互作用，我们应用了一种称为体内诱导抗原技术（IVIAT）的免疫筛选技术，以鉴定携带者特有的潜在生物标志物。IVIAT 可识别在体内环境中特异性表达的体液免疫反应性细菌抗原，我们假设在人类胆道中存活的伤寒沙门氏菌可能表达独特的抗原表型。在携带人群中具有免疫反应性但在伤寒流行地区的健康人群中无免疫反应性的 13 种伤寒沙门氏菌抗原被鉴定出来。鉴定出的抗原包括一些假定的膜蛋白、脂蛋白和溶血素相关蛋白。在我们的筛选中，一个具有 ATP 结合基序的未表征蛋白 YncE（STY1479）给出了突出的反应。将胆道中含有伤寒沙门氏菌的患者与胆道中不含有伤寒沙门氏菌的患者、急性伤寒患者和居住在伤寒流行地区的健康对照者进行比较，分析他们对 YncE 的反应。10 名慢性携带者中有 7 名（70%）、8 名胆道培养阴性对照者中无 1 名（0%）、8 名健康孟加拉人中无 1 名（0%）和 8 名急性伤寒患者中有 1 名（12.5%）在血液中检测到可检测的抗 YncE IgG。也存在 IgA 反应。
结论/意义：进一步评估 IVIAT 鉴定的 YncE 和其他抗原可能会导致开发出改进的诊断检测方法，以识别无症状伤寒沙门氏菌携带者。
