Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
Parasitology. 2022 Sep;149(11):1411-1418. doi: 10.1017/S0031182022000816. Epub 2022 Jun 15.
spp. are parasitic protozoa that cause leishmaniasis, a disease endemic in 98 countries. promastigotes are transmitted by the vector and differentiate into amastigotes within phagocytic cells of the vertebrate host. To survive in multiple and hostile environments, the parasite has several virulence factors. Oligopeptidase B (OPB) is a serine peptidase present in prokaryotes, some eukaryotes and some higher plants. It has been considered a virulence factor in trypanosomatids, but only a few studies, performed with Old World species, analysed its role in virulence or infectivity. () is an important agent of cutaneous leishmaniasis in Brazil. The () OPB encoding gene has been sequenced and analysed but has never been expressed. In this work, we produced recombinant () OPB and showed that its pH preferences, and inhibition patterns are similar to those reported for () and () OPBs. Since is known to secrete OPB, we performed infection assays using the recombinant enzyme. Our results showed that active OPB increased infection by () when present before and throughout infection. Our findings suggest that OPB is relevant to () infection, and that potential drugs acting through OPB will probably be effective for Old and New World species. OPB inhibitors may eventually be explored for leishmaniasis chemotherapy.
种是寄生的原生动物,可引起利什曼病,该病在 98 个国家流行。前鞭毛体由媒介传播,并在脊椎动物宿主的吞噬细胞内分化为无鞭毛体。为了在多个敌对环境中生存,寄生虫有几种毒力因子。寡肽酶 B (OPB) 是一种存在于原核生物、一些真核生物和一些高等植物中的丝氨酸肽酶。它被认为是原生动物中的一种毒力因子,但只有少数针对旧世界物种的研究分析了其在毒力或感染力中的作用。是巴西皮肤利什曼病的重要病原体。已对 () 编码基因进行了测序和分析,但从未进行过表达。在这项工作中,我们生产了重组 () OPB,并表明其 pH 偏好、和抑制模式与 () 和 () OPB 的报道相似。由于已知 () 会分泌 OPB,我们使用重组酶进行了感染实验。我们的结果表明,当存在于感染前后和整个过程中时,活性 OPB 增加了 () 的感染。我们的发现表明 OPB 与 () 感染有关,并且通过 OPB 作用的潜在药物可能对旧世界和新世界的物种都有效。OPB 抑制剂最终可能会被探索用于利什曼病的化学疗法。