Khafri Abolfazl, Aghaiypour Khosrow, Peerayeh Shahin Najar, Ghorbani Reihaneh
Department of Bacteriology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Avicenna J Med Biotechnol. 2011 Jan;3(1):19-24.
Bordetella pertussis is a gram negative bacterium that causes respiratory tract infection in human (whooping cough). Pertussis toxin (PT) is the main component of current acellular pertussis vaccine and the S1 (subunit1) is the main immunogenic part of it. Thus, S1 has been the target of many studies as a potent candidate of acellular vaccine against Bordetella pertussis, lacking the side effects of whole cell based ones. S1 gene was amplified and inserted in three expression vectors including pET-14b, pET-22b(+) and pAED4. The possibility and level of expression of these constructs were investigated in BL21 (DE3) strain of Escherichia coli (E.coli) as expression host. The highest expression was in pET-22b(+)-S1. Best expression achieved 6 hr post induction with 0.2 mM IPTG in LB broth containing ampicillin, at 30°C with shaking (250 rpm). Recombinant S1 protein was observed in two distinct separated proteins with 28 and 31 kDa estimated molecular weight. In spite of toxicity of PT and S1 in the E.coli, considerable amount of S1 was expressed in E.coli. Two rS1 bands were detected on SDS-PAGE. Both were confirmed as S1 in western blot with specific monoclonal and polyclonal antibodies against pertussis toxin. Appearance of two distinct bands could be the result of leader peptidase activity or nonspecific peptidase from E.coli on recombinant S1. As the recombinant S1 is a suitable antigen for studies as a candidate acellular vaccine or development of ELISA for detection of Bordetella pertussis, further studies are underway.
百日咳博德特氏菌是一种革兰氏阴性细菌,可引起人类呼吸道感染(百日咳)。百日咳毒素(PT)是当前无细胞百日咳疫苗的主要成分,其S1(亚基1)是主要的免疫原性部分。因此,S1作为一种有效的无细胞百日咳疫苗候选物,一直是许多研究的目标,它没有全细胞疫苗的副作用。扩增S1基因并将其插入包括pET-14b、pET-22b(+)和pAED4在内的三种表达载体中。在大肠杆菌BL21(DE3)菌株作为表达宿主中研究了这些构建体的表达可能性和水平。最高表达量出现在pET-22b(+)-S1中。在含有氨苄青霉素的LB肉汤中,于30°C振荡(250 rpm)条件下,用0.2 mM异丙基-β-D-硫代半乳糖苷(IPTG)诱导6小时后实现最佳表达。在估计分子量为28 kDa和31 kDa的两种不同的分离蛋白中观察到重组S1蛋白。尽管PT和S1对大肠杆菌有毒性,但仍在大肠杆菌中表达了相当数量的S1。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)上检测到两条rS1条带。在western blot中,用针对百日咳毒素的特异性单克隆和多克隆抗体证实两者均为S1。出现两条不同的条带可能是由于大肠杆菌的前导肽酶活性或非特异性肽酶作用于重组S1所致。由于重组S1是作为无细胞疫苗候选物进行研究或开发用于检测百日咳博德特氏菌的酶联免疫吸附测定(ELISA)的合适抗原,因此进一步的研究正在进行中。