Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. joanna.koziel @ uj.edu.pl
J Innate Immun. 2010;2(3):288-93. doi: 10.1159/000281881. Epub 2010 Feb 4.
Tannerella forsythia is a gram-negative bacterium strongly associated with the development and/or progression of periodontal disease. Here, we have shown that a newly characterized matrix metalloprotease-like enzyme, referred to as karilysin, efficiently cleaved the antimicrobial peptide LL-37, significantly reducing its bactericidal activity. This may contribute to the resistance of T. forsythia to the antibacterial activity of LL-37, since their vitality was found not to be affected by LL-37 at concentrations up to 2.2 muM. Furthermore, proteolysis of LL-37 by karilysin not only abolished its ability to bind lipopolysaccharide (LPS) to quench endotoxin-induced proinflammatory activity, but LL-37 cleavage also caused the release of active endotoxin from the LPS/LL-37 complex. Proteolytic inactivation of LL-37 bactericidal activity by karilysin may protect LL-37-sensitive species in the subgingival plaque and maintain the local inflammatory reaction driven by LPS from gram-negative bacteria. Consequently, the karilysin protease may directly contribute to periodontal tissue damage and the development and/or progression of chronic periodontitis.
福赛拟杆菌是一种革兰氏阴性菌，与牙周病的发生和/或发展密切相关。在这里，我们已经表明，一种新表征的基质金属蛋白酶样酶，称为卡里林，能够有效地切割抗菌肽 LL-37，显著降低其杀菌活性。这可能有助于福赛拟杆菌对 LL-37 的抗菌活性产生耐药性，因为在高达 2.2 μM 的浓度下，它们的活力并未受到 LL-37 的影响。此外，卡里林对 LL-37 的蛋白水解不仅消除了其结合脂多糖 (LPS) 以抑制内毒素诱导的促炎活性的能力，而且 LL-37 切割还导致活性内毒素从 LPS/LL-37 复合物中释放出来。卡里林对 LL-37 杀菌活性的蛋白水解失活可能会保护龈下斑块中对 LL-37 敏感的物种，并维持由革兰氏阴性菌 LPS 驱动的局部炎症反应。因此，卡里林蛋白酶可能直接导致牙周组织损伤以及慢性牙周炎的发生和/或发展。
