Ochoa Theresa J, Brown Eric L, Guion Chase E, Chen Jane Z, McMahon Robert J, Cleary Thomas G
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Biochem Cell Biol. 2006 Jun;84(3):369-76. doi: 10.1139/o06-053.
We previously demonstrated that lactoferrin inhibits adherence of enteropathogenic Escherichia coli to HEp-2 cells and decreases invasiveness of Shigella flexneri in HeLa cells by disruption of the type III secretory system (TTSS) of both enteropathogens. To determine whether these effects were specific to the TTSS, we assessed the activity of bovine lactoferrin on enteroaggregative E. coli (EAEC), enteropathogens whose virulence is not TTSS dependent. Bovine lactoferrin at a concentration of 1.0 and 0.1 mg/mL inhibited EAEC growth. Saturation with iron reversed the bacteriostatic effect. Lactoferrin under nonbacteriostatic conditions decreased EAEC adherence to HEp-2 cells as evaluated by microscopy and CFUs; this effect was not iron dependent. Lactoferrin inhibited EAEC biofilm formation and increased autoagglutination. Lactoferrin blocks EAEC adherence by inducing release and degradation of aggregative adherence fimbria, a key element of EAEC pathogenesis. We hypothesized that lactoferrin binding to lipid A of lipopolysaccharide disrupts the virulence proteins anchored to the bacterial outermembrane. These data suggest that the effect of lactoferrin on surface proteins is not restricted to organisms having a TTSS.
我们之前证明，乳铁蛋白可通过破坏两种肠道病原体的III型分泌系统（TTSS），抑制致病性大肠杆菌对HEp-2细胞的黏附，并降低福氏志贺菌在HeLa细胞中的侵袭性。为了确定这些作用是否对TTSS具有特异性，我们评估了牛乳铁蛋白对肠聚集性大肠杆菌（EAEC）的活性，EAEC是一种毒力不依赖于TTSS的肠道病原体。浓度为1.0和0.1 mg/mL的牛乳铁蛋白可抑制EAEC生长。铁饱和可逆转抑菌作用。通过显微镜检查和菌落形成单位评估，在非抑菌条件下乳铁蛋白可降低EAEC对HEp-2细胞的黏附；这种作用不依赖于铁。乳铁蛋白可抑制EAEC生物膜形成并增加自凝作用。乳铁蛋白通过诱导聚集性黏附菌毛（EAEC发病机制的关键要素）的释放和降解来阻断EAEC黏附。我们推测乳铁蛋白与脂多糖的脂质A结合会破坏锚定在细菌外膜上的毒力蛋白。这些数据表明，乳铁蛋白对表面蛋白的作用并不局限于具有TTSS系统的生物体。
