Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-05-26 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1573618

Chandra Kanta Bhusal, Shweta Sinha, Davinder Kaur, Rakesh Sehgal

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Abstract

Leishmaniasis remains a significant global health challenge, with over a billion people at risk of infection and limited effective treatment options due to escalating drug resistance. This review explores the underlying mechanisms of drug resistance in Leishmania species, focusing on genomic plasticity as a driving factor for survival and adaptation. Key mechanisms, including genetic mutations, gene amplification, chromosomal rearrangements, and efflux transporters, contribute to the parasite's ability to evade existing therapies. Advances in genomic and proteomic studies have provided deeper insights into these resistance pathways, enabling the development of novel therapeutic strategies. Additionally, this review highlights current therapeutic approaches, including combination therapies and potential new drug candidates, that address multidrug resistance and explore the vulnerabilities of Leishmania. Understanding these mechanisms and their clinical implications is essential for developing targeted interventions that improve treatment outcomes and combat resistance in leishmaniasis.

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揭示利什曼病的耐药性：基因组适应和新兴疗法。

利什曼病仍然是一项重大的全球卫生挑战，有超过10亿人面临感染风险，由于耐药性不断升级，有效的治疗选择有限。这篇综述探讨了利什曼原虫耐药的潜在机制，重点是基因组可塑性作为生存和适应的驱动因素。关键机制，包括基因突变、基因扩增、染色体重排和外排转运体，有助于寄生虫逃避现有治疗的能力。基因组学和蛋白质组学研究的进展为这些耐药途径提供了更深入的见解，使新的治疗策略得以发展。此外，本综述强调了目前的治疗方法，包括联合治疗和潜在的新候选药物，这些方法解决了多药耐药问题，并探讨了利什曼原虫的脆弱性。了解这些机制及其临床意义对于制定有针对性的干预措施以改善治疗结果和对抗利什曼病的耐药性至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.