Genetic coping mechanisms observed in Leishmania tropica, from the Middle East region, enhance the survival of the parasite after drug exposure.

Autor: Glans H; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.; Division of Dermatology and Venerology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden., Matos GM; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Bradley M; Division of Dermatology and Venerology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden., Downing T; School of Biotechnology, Dublin City University, Dublin, Ireland.; The Pirbright Institute, Woking, United Kingdom., Andersson B; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Dec 03; Vol. 19 (12), pp. e0310821. Date of Electronic Publication: 2024 Dec 03 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0310821
Abstrakt: Introduction: Cutaneous leishmaniasis caused by L. tropica is common in the Middle East and treatment failure and drug resistance are known to occur. Several genetic mechanisms: aneuploidy, recombination and loss of heterozygosity, single nucleotide polymorphism (SNP) changes, copy number variation (CNV), and mutation of the H locus associated with drug resistance have been described.
Materials and Methods: We studied SNP and CNV patterns in 22 isolates of L. tropica from Afghanistan, Iran and Syria in a geographic, phylogenetic and antimony exposure context.
Results: A high SNP frequency was observed in isolates from Syria on chromosome 23, including the H locus, linked to different ancestry at that chromosome segment. Among the isolates from Afghanistan and Iran, an elevated frequency of nonsynonymous SNPs was observed on several chromosomes. Changes in CNV patterns were seen in isolates exposed to drug pressure, especially for the ferric iron reductase gene. Expanded genes were categorised into five functional categories: translational elongation, mitochondrial transmembrane transport, positive regulation of cellular component organisation, response to stimulus and response to hypoxia. No CNV was identified at the H locus, the MAPK1 gene, the APQ1 gene, nor chromosomes 23, 31 or 36 regardless of previous antimonial exposure.
Discussion: In our study, Leishmania tropica had a jump in the nonsynonymous SNP rates at chromosome 23, including the H locus. CNV was observed among isolates exposed to antimonials, especially involving the gene encoding a ferric iron reductase. Several essential genetic coping mechanisms in the cell were enhanced when exposed to antimony, possibly for the survival of the parasite. Our work supports the perspective that Leishmania uses several mechanisms to adapt to environmental changes and drug exposure.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Glans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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