Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil; Departamento de Medicina Veterinária Preventiva e Saúde Animal, Faculdade de Medicina Veterinária e Zootecnia da USP, São Paulo, Brazil.
Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
Microb Pathog. 2021 Jan;150:104704. doi: 10.1016/j.micpath.2020.104704. Epub 2020 Dec 24.
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.
钩端螺旋体是一种需氧、革兰氏阴性的螺旋体，具有很强的侵袭能力。致病性钩端螺旋体分泌蛋白酶，可使多种宿主蛋白失活，包括细胞外基质分子和人体补体系统分子。这种策略被几种具有医学重要性的病原体所采用，有助于细菌入侵和免疫逃避。在目前的工作中，我们提供了证据表明，钩端螺旋体蛋白酶也靶向人类防御素（LL-37），这是一种在先天免疫反应中起重要作用的抗菌肽。通过使用六种钩端螺旋体菌株，四种致病性和两种腐生性，我们证明了存在于致病性菌株上清液中的蛋白酶能够以时间依赖性方式降解 LL-37，而两种腐生性菌株的上清液中未观察到蛋白水解降解。使用 1,10-邻菲啰啉抑制剂可以阻止 LL-37 的失活，因此表明金属蛋白酶参与了这一过程。此外，还评估了 LL-37 对两种钩端螺旋体菌株的抗菌活性。与腐生性菌株相比，致病性菌株对肽的作用表现出更大的抗性。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武器库的一部分，我们假设其被细菌失活可能会影响疾病的结果。
