Genetic Diversity, Plasticity, and Gene Manipulation Strategies in Leishmania: Implications for Treatment and Vaccine Research

Leishmaniasis is a neglected tropical disease (NTD) that remains a significant global health challenge. While a small number of drugs are clinically effective, their use is constrained by toxicity, high cost, and emerging drug resistance. Furthermore, no licensed human vaccine is currently available. Leishmania exhibits extensive genomic plasticity, primarily through aneuploidy, gene copy number variations (CNVs), and subtelomeric amplifications, which confer remarkable flexibility and rapid adaptation to adverse environments, such as those encountered within the host or during drug treatment. Moreover, the extensive genetic diversity and plasticity of Leishmania enable it to rapidly adjust gene expression in response to environmental changes, facilitating adaptation to various stressors, including host immune responses and drug exposure. This adaptability significantly complicates effective treatment. In addition to vertical gene transfer, genetic exchange through hybridization and karyotypic instability are well-documented mechanisms that enhance the parasite's capacity to adapt to environmental stress. The role of horizontal gene transfer remains under investigation. This mini-review highlights the unique genomic features of Leishmania, particularly its genetic flexibility and unconventional mechanisms of gene expression regulation, such as aneuploidy and CNVs. It also examines major genetic manipulation tools used to investigate parasite biology, while discussing their inherent limitations. Understanding gene function is essential yet remains challenging due to the parasite's atypical genome organization and regulatory mechanisms. A deeper comprehension of Leishmania genetics is therefore crucial for the rational design of effective drugs and vaccines.

کلیدواژه ها:

Leishmaniasis ، Leishmania ، Genetic diversity ، Genomic plasticity ، Treatment ، Vaccine ، Gene manipulation