Immunoproteomic analysis reveals a convergent humoral response signature in the Sporothrix schenckii complex.
摘要：
Sporotrichosis is a polymorphic disease that affects both humans and animals worldwide. The fungus gains entry into a warm-blooded host through minor trauma to the skin, typically by contaminated vegetation or by scratches and bites from a diseased cat. Cellular and humoral responses triggered upon pathogen introduction play important roles in the development and severity of the disease. We investigated molecules expressed during the host-parasite interplay that elicit the humoral response in human sporotrichosis. For antigenic profiling, Sporothrix yeast cell extracts were separated by two-dimensional (2D) gel electrophoresis and probed with pooled sera from individuals with fixed cutaneous and lymphocutaneous sporotrichosis. Thirty-five IgG-seroreactive spots were identified as eight specific proteins by MALDI-ToF/MS. Remarkable cross-reactivity among Sporothrix brasiliensis, Sporothrix schenckii, and Sporothrix globosa was noted and antibodies strongly reacted with the 70-kDa protein (gp70), irrespective of clinical manifestation. Gp70 was successfully identified in multiple spots as 3-carboxymuconate cyclase. In addition, 2D-DIGE characterization suggested that the major antigen of sporotrichosis undergoes post-translational modifications involving glycosylation and amino acid substitution, resulting in at least six isoforms and glycoforms that were present in the pathogenic species but absent in the ancestral non-virulent Sporothrix mexicana. Although a primary environmental function related to the benzoate degradation pathway of aromatic polymers has been attributed to orthologs of this molecule, our findings support the hypothesis that gp70 is important for pathogenesis and invasion in human sporotrichosis. We propose a diverse panel of new putative candidate molecules for diagnostic tests and vaccine development. Outbreaks due to Sporothrix spp. have emerged over time, affecting thousands of patients worldwide. A sophisticated host-pathogen interplay drives the manifestation and severity of infection, involving immune responses elicited upon traumatic exposure of the skin barrier to the pathogen followed by immune evasion. Using an immunoproteomic approach we characterized proteins of potential significance in pathogenesis and invasion that trigger the humoral response during human sporotrichosis. We found gp70 to be a cross-immunogenic protein shared among pathogenic Sporothrix spp. but absent in the ancestral environmental S. mexicana, supporting the hypothesis that gp70 plays key roles in pathogenicity. For the first time, we demonstrate with 2D-DIGE that post-translational modifications putatively involve glycosylation and amino acid substitution, resulting in at least six isoforms and glycoforms, all of them IgG-reactive. These findings of a convergent humoral response highlight gp70 as an important target serological diagnosis and for vaccine development among phylogenetically related agents of sporotrichosis.
收起
展开
DOI：
10.1016/j.jprot.2014.11.013
被引量：
年份：
1970
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
通过 文献互助 平台发起求助，成功后即可免费获取论文全文。
求助方法1：
知识发现用户
每天可免费求助50篇
求助方法1：
关注微信公众号
每天可免费求助2篇
求助方法2：
完成求助需要支付5财富值
您目前有 1000 财富值
相似文献(193)
参考文献(0)
引证文献(41)
来源期刊
影响因子：暂无数据
JCR分区： 暂无
中科院分区：暂无
