Pseudomonas aeruginosa Alginate Promotes Burkholderia cenocepacia Persistence in Cystic Fibrosis Transmembrane Conductance Regulator Knockout Mice
Pseudomonas aeruginosa Alginate Promotes Burkholderia cenocepacia Persistence in Cystic Fibrosis Transmembrane Conductance Regulator Knockout Mice
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DOI：
10.1128/iai.01192-09
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Sajjan, Umadevi S.
中科院分区：
文献类型：
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作者：
Chattoraj, Sangbrita S.;Murthy, Rachana;Sajjan, Umadevi S.
铜绿假单胞菌是囊性纤维化（CF）患者的主要呼吸道病原体，可促进其他机会性病原体的感染。通常感染青少年患者的新洋葱伯克霍尔德菌遇到了由粘液铜绿假单胞菌精心制作的藻酸盐。确定铜绿假单胞菌藻酸盐是否促进B。在新洋葱虫感染的小鼠中，用B感染囊性纤维化跨膜传导调节因子敲除小鼠。将新洋葱菌菌株BC 7悬浮在磷酸盐缓冲盐水（BC 7/PBS）或铜绿假单胞菌藻酸盐（BC 7/藻酸盐）中，并监测肺部细菌负荷和炎症。用BC 7/PBS感染的小鼠在3天内清除了所有细菌，并且炎症在第5天消退。相比之下，感染BC 7/藻酸盐的小鼠显示细菌的持续存在和细胞因子水平的增加长达7天。肺组织学检查表明，在BC 7/藻酸盐组中，在感染后5天和7天，在隔离区域中存在中度至重度炎症和肺实变。此外，藻酸盐降低了B的吞噬作用。在体内和体外的专业吞噬细胞cenocepacia。铜绿假单胞菌藻酸盐还降低了CF气道上皮细胞和肺泡巨噬细胞对B的促炎反应。新洋葱感染观察到的效果是特定的铜绿假单胞菌藻酸盐，因为酶降解的藻酸盐或其他多糖醛酸不促进细菌的持久性。这些观察结果表明，铜绿假单胞菌藻酸盐可以促进B。通过干扰宿主的先天防御机制感染新洋葱。
Pseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF) patients, facilitates infection by other opportunistic pathogens. Burkholderia cenocepacia, which normally infects adolescent patients, encounters alginate elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosa alginate facilitates B. cenocepacia infection in mice, cystic fibrosis transmembrane conductance regulator knockout mice were infected with B. cenocepacia strain BC7 suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosa alginate (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored. Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate showed persistence of bacteria and increased cytokine levels for up to 7 days. Histological examination of the lungs indicated that there was moderate to severe inflammation and pneumonic consolidation in isolated areas at 5 and 7 days postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis of B. cenocepacia by professional phagocytes both in vivo and in vitro. P. aeruginosa alginate also reduced the proinflammatory responses of CF airway epithelial cells and alveolar macrophages to B. cenocepacia infection. The observed effects are specific to P. aeruginosa alginate, because enzymatically degraded alginate or other polyuronic acids did not facilitate bacterial persistence. These observations suggest that P. aeruginosa alginate may facilitate B. cenocepacia infection by interfering with host innate defense mechanisms.