Leptospires are aerobic, Gram-negative spirochetes with a high invasive capacity. Pathogenic leptospires secrete proteases that inactivate a variety of host's proteins including molecules of the extracellular matrix and of the human complement system. This strategy, used by several pathogens of medical importance, contributes to bacterial invasion and immune evasion. In the current work we present evidence that Leptospira proteases also target human cathelicidin (LL-37), an antimicrobial peptide that plays an important role in the innate immune response. By using six Leptospira strains, four pathogenic and two saprophytic, we demonstrated that proteases present in the supernatants of pathogenic strains were capable of degrading LL-37 in a time-dependent manner, whereas proteolytic degradation was not observed with the supernatants of the two saprophytic strains. Inactivation of LL-37 was prevented by using the 1,10-phenanthroline inhibitor, thus suggesting the involvement of metalloproteinases in this process. In addition, the antibacterial activity of LL-37 against two Leptospira strains was evaluated. Compared to the saprophytic strain, a greater resistance of the pathogenic strain to the action of the peptide was observed. Our data suggest that the capacity to inactivate the host defense peptide LL-37 may be part of the virulence arsenal of pathogenic Leptospira, and we hypothesize that its inactivation by the bacteria may influence the outcome of the disease.

钩端螺旋体是有氧，革兰氏阴性螺旋体，具有很高的侵袭能力。致病性钩端螺旋体分泌的蛋白酶可以使多种宿主蛋白​​质失活，包括细胞外基质分子和人补体系统的分子。几种具有医学重要性的病原体使用的这种策略有助于细菌入侵和免疫逃逸。在当前的工作中，我们提供了钩端螺旋体蛋白酶也靶向人cathelicidin（LL-37）的证据，该抗菌肽在先天免疫应答中起重要作用。通过使用六个钩端螺旋体四个致病菌株和两个腐生菌株，我们证明了存在于致病菌株上清液中的蛋白酶能够以时间依赖性方式降解LL-37，而在两个腐生菌株的上清液中均未观察到蛋白水解降解。通过使用1,10-菲咯啉抑制剂可防止LL-37失活，因此表明金属蛋白酶参与了该过程。另外，评估了LL-37对两种钩端螺旋体菌株的抗菌活性。与腐生菌株相比，观察到病原菌株对肽的作用具有更大的抗性。我们的数据表明，使宿主防御肽LL-37失活的能力可能是致病性钩端螺旋体毒力库的一部分，并且我们假设细菌将其灭活可能会影响疾病的结果。