Resistance of Leishmania infantum to allopurinol is associated with chromosome and gene copy number variations including decrease in the S-adenosylmethionine synthetase (METK) gene copy number

International Journal for Parasitology. Drugs and Drug Resistance
Daniel Yasur-LandauGad Baneth

Abstract

Leishmania infantum is one of the causative agents of visceral leishmaniasis (VL), a widespread, life-threatening disease. This parasite is responsible for the majority of human VL cases in Brazil, the Middle East, China, Central Asia and the Mediterranean basin. Its main reservoir are domestic dogs which, similar to human patients, may develop severe visceral disease and die if not treated. The drug allopurinol is used for the long-term maintenance of dogs with canine leishmaniasis. Following our report of allopurinol resistance in treated relapsed dogs, we investigated the mechanisms and markers of resistance to this drug. Whole genome sequencing (WGS) of clinical resistant and susceptible strains, and laboratory induced resistant parasites, was carried out in order to detect genetic changes associated with resistance. Significant gene copy number variation (CNV) was found between resistant and susceptible isolates at several loci, including a locus on chromosome 30 containing the genes LinJ.30.3550 through LinJ.30.3580. A reduction in copy number for LinJ.30.3560, encoding the S-adenosylmethionine synthetase (METK) gene, was found in two resistant clinical isolates and four induced resistant clonal strains. Using quantitativ...Continue Reading

Citations

Mar 3, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·Husein Husein-ElAhmedMartin Steinhoff
Jul 1, 2020·Antimicrobial Agents and Chemotherapy·M Van den KerkhofG Caljon
Jul 1, 2020·Microorganisms·Magali Van den KerkhofGuy Caljon
Oct 15, 2019·Frontiers in Cellular and Infection Microbiology·Fatima Conceição-Silva, Fernanda N Morgado
Jul 27, 2021·Parasite Immunology·Layana Pachêco de Araújo AlbuquerqueCarlos Henrique Nery Costa
Sep 8, 2021·Microbial Genomics·Luz H PatinoJuan David Ramírez

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Methods Mentioned

BETA
PCR

Software Mentioned

Bioconductor cn . MOPS
R scripts
gplots
JMP12
MOPS
R
Prism
StepOne
SOAP Analysis Package

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