Scholarlink

<p>Leishmaniasis affects millions of people worldwide and is caused by obligate intracellular protozoan parasites transmitted through infected phlebotomine sand flies. Clinical outcomes range from self-healing cutaneous lesions to fatal visceral disease across twenty recognised human-pathogenic species. The <i>Leishmania</i> secretome contains virulence factors crucial for establishing infection, modulating host immunity, and promoting parasite survival within macrophages. Previous proteomic studies have characterised candidate secreted proteins across multiple species, identifying a conserved core secretome predominantly released via extracellular vesicles through non-classical pathways. However, large portions of the predicted proteome remain experimentally unvalidated. To uncover overlooked proteins, we conducted a comprehensive proteogenomic analysis using publicly available mass spectrometry datasets. Custom six-frame translated genome databases were generated for seven reference <i>Leishmania</i> species, enabling the identification of genome search-specific peptides. This approach helps to detect the novel candidate secreted proteins that have been missed in previous secretome research, together with low-abundance features, hypothetical proteins and the proteins that are from the canonical translation procedures. This proteogenomic study identified 469 candidate secreted proteins in the seven <i>Leishmania</i> species that were not reported previously. The proteins were significantly explored and validated in the <i>Leishmania</i> proteome and disclose a higher level of functional diversity. The visceralising species were abundant in ATP-binding proteins and oxidoreductases, while the cutaneous species were represented with proteasome-rich secretome profiles. The identification of these further candidate secreted proteins highlights the boundaries of previous studies and emphasises the higher resolution provided by the proteogenomic approaches. The species-specific categorical and functional differences explored in this study can contribute to diverse tissue tropisms, host–pathogen interactions and the clinical indicators of leishmaniasis. The newly identified proteins in this study likely include previously unidentified virulence factors with potential significance for parasite variations, pathogenesis, and therapeutic interference. This study reveals that the proteogenomic analysis is a prevailing approach for exploring the secretome of <i>Leishmania</i> species. These findings advance the understanding of parasite evolution and biology by identifying 469 novel putative secreted proteins and detecting the significant species-specific functional diversity; they also highlight potential indicators for future functional research and therapeutic interventions.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mapping the hidden secretome in Leishmania parasites using a proteogenomics approach

  • 期刊论文

  • 发表日期：

    2026年6月23日

查看全文
  • Soumi Chowdhury,
  • Karthick Vasudevan,
  • Shubhankar Pawar,
  • Molieswar Jaikumar,
  • Piyush Mohapatra,
  • Nitin Tupperwar,
  • Harsh Pawar

摘要

Leishmaniasis affects millions of people worldwide and is caused by obligate intracellular protozoan parasites transmitted through infected phlebotomine sand flies. Clinical outcomes range from self-healing cutaneous lesions to fatal visceral disease across twenty recognised human-pathogenic species. The Leishmania secretome contains virulence factors crucial for establishing infection, modulating host immunity, and promoting parasite survival within macrophages. Previous proteomic studies have characterised candidate secreted proteins across multiple species, identifying a conserved core secretome predominantly released via extracellular vesicles through non-classical pathways. However, large portions of the predicted proteome remain experimentally unvalidated. To uncover overlooked proteins, we conducted a comprehensive proteogenomic analysis using publicly available mass spectrometry datasets. Custom six-frame translated genome databases were generated for seven reference Leishmania species, enabling the identification of genome search-specific peptides. This approach helps to detect the novel candidate secreted proteins that have been missed in previous secretome research, together with low-abundance features, hypothetical proteins and the proteins that are from the canonical translation procedures. This proteogenomic study identified 469 candidate secreted proteins in the seven Leishmania species that were not reported previously. The proteins were significantly explored and validated in the Leishmania proteome and disclose a higher level of functional diversity. The visceralising species were abundant in ATP-binding proteins and oxidoreductases, while the cutaneous species were represented with proteasome-rich secretome profiles. The identification of these further candidate secreted proteins highlights the boundaries of previous studies and emphasises the higher resolution provided by the proteogenomic approaches. The species-specific categorical and functional differences explored in this study can contribute to diverse tissue tropisms, host–pathogen interactions and the clinical indicators of leishmaniasis. The newly identified proteins in this study likely include previously unidentified virulence factors with potential significance for parasite variations, pathogenesis, and therapeutic interference. This study reveals that the proteogenomic analysis is a prevailing approach for exploring the secretome of Leishmania species. These findings advance the understanding of parasite evolution and biology by identifying 469 novel putative secreted proteins and detecting the significant species-specific functional diversity; they also highlight potential indicators for future functional research and therapeutic interventions.

Graphical abstract