Chiu Cheng-Hsun, Wong Simon, Hancock Robert E W, Speert David P
Department of Paediatrics, Chang Gung Children's Hospital, Kweishan 333, Taoyuan, Taiwan1.
The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, UK2.
Microbiology (Reading). 2001 Oct;147(Pt 10):2651-2658. doi: 10.1099/00221287-147-10-2651.
Adherence of Burkholderia cepacia to cells of the respiratory tract of patients with cystic fibrosis (CF) appears to be a necessary precondition for colonization and infection. To date, no effective anti-adhesive strategy has been devised for preventing B. cepacia infection in CF patients. It was found in this study that B. cepacia adhered to respiratory epithelial cells both in vitro and in vivo. However, strains with cable-like pili (Cbl) exhibited the typical clump formation on pneumocytes, whereas non-cable piliated strains predominantly showed single-cell adherence. Dextrans (nominally 4000-10000 Da) significantly inhibited adhesion of B. cepacia to A549 pneumocytes. When compared on an equal weight basis, the nominally 10000 Da dextran was most inhibitory. A dose-dependent inhibitory effect (up to 80 mg ml(-1)) was observed for most strains. Dextran exerted less of an anti-adhesive effect on the two Cbl+ strains than on the others which were Cbl-. Dextrans appeared to block the adherence in a non-specific fashion, as shown by the observations that the inhibitory effect was readily reversible and oligosaccharides composed of 2-4 glucose units with the same alpha-1,6 linkage were not inhibitory. The mean molecular masses of dextrans used in this study, as determined by gel filtration and MS, were approximately 10-fold lower than those indicated by the manufacturers. Our data suggest that dextran of nominal molecular mass 4000 Da at a concentration of 40 mg ml(-1) (10 mM according to manufacturer's quoted molecular mass) or more may be useful in patients with CF to prevent colonization and infection with B. cepacia.
洋葱伯克霍尔德菌黏附于囊性纤维化(CF)患者呼吸道细胞似乎是定植和感染的必要前提条件。迄今为止,尚未设计出有效的抗黏附策略来预防CF患者的洋葱伯克霍尔德菌感染。本研究发现,洋葱伯克霍尔德菌在体外和体内均能黏附于呼吸道上皮细胞。然而,具有丝状菌毛(Cbl)的菌株在肺细胞上表现出典型的聚集形成,而非丝状菌毛菌株主要表现为单细胞黏附。葡聚糖(标称分子量4000 - 10000 Da)显著抑制洋葱伯克霍尔德菌对A549肺细胞的黏附。在等重量基础上比较时,标称10000 Da的葡聚糖抑制作用最强。大多数菌株观察到剂量依赖性抑制作用(高达80 mg ml⁻¹)。与其他Cbl⁻菌株相比,葡聚糖对两种Cbl⁺菌株的抗黏附作用较小。葡聚糖似乎以非特异性方式阻断黏附,如观察到抑制作用易于逆转以及由2 - 4个具有相同α-1,6连接的葡萄糖单元组成的寡糖无抑制作用所示。通过凝胶过滤和质谱测定,本研究中使用的葡聚糖的平均分子量比制造商标明的低约10倍。我们的数据表明,标称分子量4000 Da、浓度为40 mg ml⁻¹(根据制造商引用的分子量为10 mM)或更高的葡聚糖可能对CF患者预防洋葱伯克霍尔德菌的定植和感染有用。