Lee Peter, Faubert Gaétan M
Institute of Parasitology, McGill University, Macdonald Campus, 21 111 Lakeshore Rd, Ste-Anne de Bellevue, Québec H9X 3V9, Canada.
Microbiology (Reading). 2006 Jul;152(Pt 7):1981-1990. doi: 10.1099/mic.0.28877-0.
In this study, Lactococcus lactis was engineered to express Giardia lamblia cyst wall protein 2 (CWP2) at three different subcellular locations, intracellular, secreted or cell-surface-anchored, using nisin as an inducing agent. CWP2 expression did not appear to be detrimental to L. lactis viability. No particular subcellular location of CWP2 expression offered any advantages over the others with respect to decreased toxicity towards the bacteria. All recombinant lactococci experienced a similar reduction in growth rate when induced. It was determined whether recombinant lactococcal cells engineered for cell surface expression of CWP2 were capable of inducing a CWP2-specific mucosal IgA antibody response. Recombinant lactococci were successful at inducing CWP2-specific IgA antibodies. Moreover, in a pilot challenge experiment, mice immunized with these recombinant lactococci demonstrated a significant (63 %) reduction in cyst output. Thus, it has been demonstrated that G. lamblia CWP2 may be expressed in L. lactis and that recombinant lactococcal cells elicit Giardia-specific antibodies which reduce cyst shedding in a murine model.
在本研究中,利用乳链菌肽作为诱导剂,对乳酸乳球菌进行工程改造,使其在细胞内、分泌型或细胞表面锚定这三个不同的亚细胞位置表达蓝氏贾第鞭毛虫囊壁蛋白2(CWP2)。CWP2的表达似乎对乳酸乳球菌的活力没有损害。就降低对细菌的毒性而言,CWP2表达的特定亚细胞位置并未显示出比其他位置有任何优势。诱导时,所有重组乳球菌的生长速率都出现了类似程度的降低。研究确定了经工程改造用于在细胞表面表达CWP2的重组乳球菌细胞是否能够诱导产生CWP2特异性的黏膜IgA抗体反应。重组乳球菌成功诱导产生了CWP2特异性IgA抗体。此外,在一项初步攻毒实验中,用这些重组乳球菌免疫的小鼠粪便中包囊排出量显著减少(63%)。因此,已证明蓝氏贾第鞭毛虫CWP2可在乳酸乳球菌中表达,并且重组乳球菌细胞能引发贾第虫特异性抗体,从而减少小鼠模型中的包囊排出。