Raffatellu Manuela, Sun Yao-Hui, Wilson R Paul, Tran Quynh T, Chessa Daniela, Andrews-Polymenis Helene L, Lawhon Sara D, Figueiredo Josely F, Tsolis Renée M, Adams L Garry, Bäumler Andreas J
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
Infect Immun. 2005 Dec;73(12):7817-26. doi: 10.1128/IAI.73.12.7817-7826.2005.
Salmonella enterica serotype Typhi is a strictly human adapted pathogen that does not cause disease in nonprimate vertebrate hosts, while Salmonella enterica serotype Typhimurium is a broad-host-range pathogen. Serotype Typhi lacks some of the proteins (effectors) exported by the invasion-associated type III secretion system that are required by serotype Typhimurium for eliciting fluid secretion and inflammation in bovine ligated ileal loops. We investigated whether the remaining serotype Typhi effectors implicated in enteropathogenicity (SipA, SopB, and SopD) are functionally exchangeable with their serotype Typhimurium homologues. Serotype Typhi elicited fluid accumulation in bovine ligated ileal loops at levels similar to those elicited by a noninvasive serotype Typhimurium strain (the sipA sopABDE2 mutant) or by sterile culture medium. However, introduction of the cloned serotype Typhi sipA, sopB, and sopD genes complemented the ability of a serotype Typhimurium sipA sopABDE2 mutant to elicit fluid secretion in bovine ligated ileal loops. Introduction of the cloned serotype Typhi sipA, sopB, and sopD genes increased the invasiveness of a serotype Typhimurium sipA sopABDE2 mutant for human colon carcinoma epithelial (HT-29 and T84) cells and bovine kidney (MDBK) cells. Translational fusions between the mature TEM-1 beta-lactamase reporter and SipA or SopD demonstrated that serotype Typhi translocates these effectors into host cells. We conclude that the inability of serotype Typhi to cause fluid accumulation in bovine ligated ileal loops is not caused by a functional alteration of its SipA, SopB, and SopD effector proteins with respect to their serotype Typhimurium homologues.
伤寒沙门氏菌血清型伤寒杆菌是一种严格适应人类的病原体，不会在非灵长类脊椎动物宿主中引发疾病，而鼠伤寒沙门氏菌血清型鼠伤寒杆菌是一种宿主范围广泛的病原体。伤寒杆菌血清型缺乏一些由侵袭相关III型分泌系统输出的蛋白质（效应器），而鼠伤寒杆菌血清型需要这些蛋白质来引发牛结扎回肠袢中的液体分泌和炎症。我们研究了与肠道致病性相关的其余伤寒杆菌血清型效应器（SipA、SopB和SopD）是否与其鼠伤寒杆菌血清型同源物在功能上可互换。伤寒杆菌血清型在牛结扎回肠袢中引发的液体蓄积水平与非侵袭性鼠伤寒杆菌血清型菌株（sipA sopABDE2突变体）或无菌培养基引发的水平相似。然而，克隆的伤寒杆菌血清型sipA、sopB和sopD基因的引入补充了鼠伤寒杆菌血清型sipA sopABDE2突变体在牛结扎回肠袢中引发液体分泌的能力。克隆的伤寒杆菌血清型sipA、sopB和sopD基因的引入增加了鼠伤寒杆菌血清型sipA sopABDE2突变体对人结肠癌上皮（HT-29和T84）细胞和牛肾（MDBK）细胞的侵袭性。成熟的TEM-1β-内酰胺酶报告基因与SipA或SopD之间的翻译融合表明，伤寒杆菌血清型将这些效应器转运到宿主细胞中。我们得出结论，伤寒杆菌血清型无法在牛结扎回肠袢中引起液体蓄积，并非因其SipA、SopB和SopD效应蛋白与其鼠伤寒杆菌血清型同源物相比存在功能改变所致。
