Ochoa Theresa J, Noguera-Obenza Marita, Ebel Frank, Guzman Carlos A, Gomez Henry F, Cleary Thomas G
Division of Pediatric Infectious Diseases, University of Texas-Houston Medical School, Houston, Texas 77040, USA.
Infect Immun. 2003 Sep;71(9):5149-55. doi: 10.1128/IAI.71.9.5149-5155.2003.
Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea in developing countries. EPEC uses a type III secretory system to deliver effector proteins into the host cell. These proteins cause the characteristic attaching and effacing lesion on enterocytes. Lactoferrin, a glycoprotein present in human milk, inhibits EPEC adherence to mammalian cells. To determine the effect of lactoferrin on the initial host cell attachment step that is mediated by the type III secretory system, we focused on EPEC-induced actin polymerization in HEp2 cells, on the hemolytic activity, and on measurement of E. coli secreted proteins A, B, and D (EspABD). Lactoferrin blocked EPEC-mediated actin polymerization in HEp2 cells and blocked EPEC-induced hemolysis. The mechanism of this inhibition was lactoferrin-mediated degradation of secreted proteins necessary for bacterial contact and pore formation, particularly EspB. The proteolytic effect of lactoferrin was prevented by serine protease inhibitors. This disruption of the type III secretory system implies that lactoferrin could provide broad cross protection against the enteropathogens that share this mechanism.
肠致病性大肠杆菌（EPEC）是发展中国家婴儿腹泻的重要病因。EPEC利用III型分泌系统将效应蛋白输送到宿主细胞中。这些蛋白会在肠上皮细胞上形成特征性的黏附和抹除损伤。乳铁蛋白是一种存在于人乳中的糖蛋白，可抑制EPEC对哺乳动物细胞的黏附。为了确定乳铁蛋白对由III型分泌系统介导的宿主细胞初始黏附步骤的影响，我们重点研究了EPEC诱导的HEp2细胞中的肌动蛋白聚合、溶血活性以及大肠杆菌分泌蛋白A、B和D（EspABD）的测定。乳铁蛋白可阻断EPEC介导的HEp2细胞中的肌动蛋白聚合，并阻断EPEC诱导的溶血。这种抑制作用的机制是乳铁蛋白介导的对细菌接触和孔形成所必需的分泌蛋白的降解，尤其是EspB。丝氨酸蛋白酶抑制剂可阻止乳铁蛋白的蛋白水解作用。III型分泌系统的这种破坏表明，乳铁蛋白可为具有这种机制的肠道病原体提供广泛的交叉保护。
