Russell Brooke H, Vasan Ranga, Keene Douglas R, Koehler Theresa M, Xu Yi
Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
Cell Microbiol. 2008 Apr;10(4):945-57. doi: 10.1111/j.1462-5822.2007.01098.x. Epub 2007 Dec 6.
Dissemination of Bacillus anthracis spores from the lung is a critical early event in the establishment of inhalational anthrax. We recently reported that B. anthracis could adhere to and be internalized by cultured intestinal epithelial and fibroblast cells. Here, using gentamicin protection assays and/or electron microscopy, we found that Sterne strain 7702 spores were able to adhere to and subsequently be internalized by polarized A549 cells and primary human small airway epithelial cells. We showed for the first time that internalized spores were able to survive and that spores could translocate across an A549 cell barrier from the apical side to the basolateral side without disrupting the barrier integrity, suggesting a transcellular route. In addition, dormant spores of fully virulent Ames and UT500 strains were able to adhere to A549 cells at a frequency similar to that of 7702, whereas the capsule in germinated Ames and UT500 spores prevented adherence. Fluorescence microscopy also revealed that dormant Ames spores were internalized at a frequency similar to that of 7702. These findings highlight the possibility of a novel route of dissemination in which B. anthracis utilizes epithelial cells of the lung. The implications of these results to B. anthracis pathogenesis are discussed.
炭疽芽孢杆菌孢子从肺部播散是吸入性炭疽发病早期的关键事件。我们最近报道,炭疽芽孢杆菌能够黏附于培养的肠道上皮细胞和成纤维细胞并被其内化。在此,我们通过庆大霉素保护试验和/或电子显微镜观察发现,Sterne菌株7702的孢子能够黏附于极化的A549细胞和原代人小气道上皮细胞并随后被其内化。我们首次表明,内化的孢子能够存活,且孢子能够在不破坏屏障完整性的情况下从顶端侧穿过A549细胞屏障转运至基底外侧,提示存在跨细胞途径。此外,完全有毒力的Ames菌株和UT500菌株的休眠孢子能够以与7702菌株相似的频率黏附于A549细胞,而萌发的Ames菌株和UT500菌株中的荚膜则会阻止黏附。荧光显微镜观察还显示,休眠的Ames孢子被内化的频率与7702菌株相似。这些发现突出了炭疽芽孢杆菌利用肺上皮细胞进行新型播散途径的可能性。本文讨论了这些结果对炭疽芽孢杆菌致病机制的意义。