英国牛津生物医学研究中心Malick M. Gibani研究团队，揭示了伤寒毒素在急性伤寒感染模型中的作用。 相关论文于2019年7月发表在《自然—医学》杂志上。

研究人员使用随机双盲的人伤寒沙门菌感染模型，研究了伤寒毒素在急性感染中的作用。40名健康志愿者被随机(1:1)以口服的方式感染104个集落形成单位的野生型菌株或同基因伤寒毒素缺失突变菌株(TN)。他们观察到，在感染了野生型或TN型伤寒沙门菌(21例中有15例(71%)，19例中有15例(79%)的参与者之间，伤寒感染率(38℃持续12h和/或伤寒杆菌血症)没有显著差异，P = 0.58。与野生型感染产生的菌血症持续时间（30.3小时(3.649.4)）相比，TN菌株感染组的菌血症持续时间(47.6小时(28.997.0)）明显更长，P 0.001。在野生型和TN组之间，临床症状难以区分。这些数据表明，在人类感染模型中，伤寒沙门菌感染和早期伤寒症状的发展并不需要伤寒毒素。需要进一步的临床数据来评估伤寒毒素在严重疾病或细菌携带的建立中的作用。

据了解，伤寒沙门菌是一种人类宿主限制病原体，每年约有1090万人感染伤寒。伤寒毒素被认为在疾病的发病机制、慢性感染的建立和人类宿主的限制中具有中心作用。然而，它在人类伤寒中的确切作用还没有完全确定。

附：英文原文

Title: Investigation of the role of typhoid toxin in acute typhoid fever in a human challenge model

Author: Malick M. Gibani, Elizabeth Jones, Amber Barton, Celina Jin, Juliette Meek, Susana Camara, Ushma Galal, Eva Heinz, Yael Rosenberg-Hasson, Gerlinde Obermoser, Claire Jones, Danielle Campbell, Charlotte Black, Helena Thomaides-Brears, Christopher Darlow, Christina Dold, Laura Silva-Reyes, Luke Blackwell, Maria Lara-Tejero, Xuyao Jiao, Gabrielle Stack, Christoph J. Blohmke, Jennifer Hill, Brian Angus, Gordon Dougan, Jorge Galn, Andrew J. Pollard

Issue&Volume: Volume 25 Issue 7, July 2019

Abstract: Salmonella Typhi is a human host-restricted pathogen that is responsible for typhoid fever in approximately 10.9 million people annually. The typhoid toxin is postulated to have a central role in disease pathogenesis, the establishment of chronic infection and human host restriction. However, its precise role in typhoid disease in humans is not fully defined. We studied the role of typhoid toxin in acute infection using a randomized, double-blind S. Typhi human challenge model. Forty healthy volunteers were randomized (1:1) to oral challenge with 104 colony-forming units of wild-type or an isogenic typhoid toxin deletion mutant (TN) of S. Typhi. We observed no significant difference in the rate of typhoid infection (fever 38C for 12h and/or S. Typhi bacteremia) between participants challenged with wild-type or TN S. Typhi (15 out of 21 (71%) versus 15 out of 19 (79%); P=0.58). The duration of bacteremia was significantly longer in participants challenged with the TN strain compared with wild-type (47.6 hours (28.997.0) versus 30.3(3.649.4); P  0.001). The clinical syndrome was otherwise indistinguishable between wild-type and TN groups. These data suggest that the typhoid toxin is not required for infection and the development of early typhoid fever symptoms within the context of a human challenge model. Further clinical data are required to assess the role of typhoid toxin in severe disease or the establishment of bacterial carriage.

DOI: 10.1038/s41591-019-0505-4

Source:https://www.nature.com/articles/s41591-019-0505-4