Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.
Drug resistance
Genome analysis
Leishmania
Paromomycin
Journal
Parasitology research
ISSN: 1432-1955
Titre abrégé: Parasitol Res
Pays: Germany
ID NLM: 8703571
Informations de publication
Date de publication:
Nov 2022
Nov 2022
Historique:
received:
20
01
2022
accepted:
24
08
2022
pubmed:
4
9
2022
medline:
15
10
2022
entrez:
3
9
2022
Statut:
ppublish
Résumé
In the absence of adequate diagnosis and treatment, leishmaniasis remains a major public health concern on a global scale. Drug resistance remains a key obstacle in controlling and eliminating visceral leishmaniasis. The therapeutic gap due to lack of target-specific medicine and vaccine can be minimized by obtaining parasite's genomic information. This study compared whole-genome sequence of paromomycin-resistant parasite (K133PMM) developed through in vitro adaptation and selection with sensitive Leishmania clinical isolate (K133WT). We found a large number of upstream and intergenic gene variations in K133PMM. There were 259 single nucleotide polymorphisms (SNPs), 187 insertion-deletion (InDels), and 546 copy number variations (CNVs) identified. Most of the genomic variations were found in the gene's upstream and non-coding regions. Ploidy estimation revealed chromosome 5 in tetrasomy and 6, 9, and 12 in trisomy, uniquely in K133PMM. These contain the genes for protein degradation, parasite motility, autophagy, cell cycle maintenance, and drug efflux membrane transporters. Furthermore, we also observed reduction in ploidy of chromosomes 15, 20, and 23, in the resistant parasite containing mostly the genes for hypothetical proteins and membrane transporters. We chronicled correlated genomic conversion and aneuploidy in parasites and hypothesize that this led to rapid evolutionary changes in response to drug induced pressure, which causes them to become resistant.
Identifiants
pubmed: 36056959
doi: 10.1007/s00436-022-07645-x
pii: 10.1007/s00436-022-07645-x
doi:
Substances chimiques
Membrane Transport Proteins
0
Paromomycin
61JJC8N5ZK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3121-3132Subventions
Organisme : Indian Council of Medical Research
ID : 6/9-7(188)2018-ECDII
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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