Shimomura Hirofumi, Matsuura Motohiro, Saito Shinji, Hirai Yoshikazu, Isshiki Yasunori, Kawahara Kazuyoshi
Division of Bacteriology, Department of Infection and Immunity, Jichi Medical School, Tochigi 239-0498, Japan.
Infect Immun. 2003 Sep;71(9):5225-30. doi: 10.1128/IAI.71.9.5225-5230.2003.
We have demonstrated that lipopolysaccharide (LPS) obtained from Burkholderia cepacia, an important opportunistic pathogen, has unique characteristics in both structure and activity. One of the structural characteristics is that the B. cepacia LPS has 4-amino-4-deoxy-L-arabinose (Ara4N) in its inner core region. Polymyxin B (PmxB) is known to act as an LPS antagonist, but LPS with Ara4N is suggested to be PmxB resistant by decreasing the binding capability of PmxB. Interaction of B. cepacia LPS with PmxB was investigated and compared with that of a reference LPS of Salmonella enterica serovar Abortusequi, referred to hereafter as the reference LPS. B. cepacia LPS suffered no suppressive effect of PmxB in its activity to stimulate murine peritoneal macrophages for induction of tumor necrosis factor alpha (TNF-alpha) and IL-6 even when the activity of the reference LPS was completely suppressed. A characteristic of B. cepacia LPS is that it has selectively weak interleukin-1 beta (IL-1 beta)-inducing activity while activity to induce TNF-alpha and IL-6 has been shown to be as strong as that of the reference LPS. Remarkably, PmxB augmented the IL-1 beta-inducing activity of B. cepacia LPS to the level of that of the reference LPS and, in contrast, completely suppressed the strong activity of the reference LPS. Using PmxB-immobilized beads, the adsorbances of these LPSs to the beads were compared, and it was found that B. cepacia LPS bound to PmxB with a high affinity similar to that of the reference LPS. These results indicate an unusual interaction of B. cepacia LPS with PmxB whereby B. cepacia LPS not only allows the binding of PmxB with high affinity, even though it contains Ara4N, but also suffers no suppressive effect of PmxB on its activity. Moreover, a remarkable increase in its IL-1 beta-inducing activity was also observed.
我们已经证明，从重要的机会致病菌洋葱伯克霍尔德菌中获得的脂多糖（LPS）在结构和活性方面都具有独特的特征。其结构特征之一是洋葱伯克霍尔德菌LPS在其内核区域含有4-氨基-4-脱氧-L-阿拉伯糖（Ara4N）。已知多粘菌素B（PmxB）可作为LPS拮抗剂，但含有Ara4N的LPS被认为可通过降低PmxB的结合能力而对PmxB产生抗性。研究了洋葱伯克霍尔德菌LPS与PmxB的相互作用，并与肠炎沙门氏菌血清型流产马流产亚种的参考LPS（以下简称参考LPS）进行了比较。即使参考LPS的活性被完全抑制，洋葱伯克霍尔德菌LPS在刺激小鼠腹腔巨噬细胞诱导肿瘤坏死因子α（TNF-α）和IL-6的活性方面也没有受到PmxB的抑制作用。洋葱伯克霍尔德菌LPS的一个特点是它具有选择性较弱的白细胞介素-1β（IL-1β）诱导活性，而诱导TNF-α和IL-6的活性已被证明与参考LPS一样强。值得注意的是，PmxB将洋葱伯克霍尔德菌LPS的IL-1β诱导活性提高到了参考LPS的水平，相反，却完全抑制了参考LPS的强活性。使用固定有PmxB的珠子，比较了这些LPS与珠子的吸附率，发现洋葱伯克霍尔德菌LPS与PmxB的结合亲和力与参考LPS相似。这些结果表明洋葱伯克霍尔德菌LPS与PmxB之间存在异常相互作用，即洋葱伯克霍尔德菌LPS不仅能使PmxB以高亲和力结合，即使它含有Ara4N，而且其活性也不受PmxB的抑制作用。此外，还观察到其IL-1β诱导活性显著增加。
