The potential therapeutic role of PTR1 gene in non-healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica.
Adult
Animals
Antiprotozoal Agents
/ pharmacology
DNA, Antisense
Drug Resistance, Microbial
/ drug effects
Female
Humans
Leishmania tropica
/ drug effects
Leishmaniasis, Cutaneous
/ drug therapy
Male
Meglumine Antimoniate
/ pharmacology
Mice, Inbred BALB C
Oxidoreductases
/ genetics
Protozoan Proteins
/ genetics
Transfection
Leishmania
antisense
pteridine reductase
resistance
transfection
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
revised:
06
11
2020
received:
04
07
2020
accepted:
12
11
2020
pubmed:
8
12
2020
medline:
5
11
2021
entrez:
7
12
2020
Statut:
ppublish
Résumé
Drug resistance is a common phenomenon frequently observed in countries where leishmaniasis is endemic. Due to the production of the pteridine reductase enzyme (PTR1), drugs lose their efficacy, and consequently, the patient becomes unresponsive to treatment. This study aimed to compare the in vitro effect of meglumine antimoniate (MA) on non- healing Leishmania tropica isolates and on MA transfected non-healing one to PTR1. Two non-healing and one healing isolates of L. tropica were collected from patients who received two courses or one cycle of intralesional MA along with biweekly liquid nitrogen cryotherapy or systemic treatment alone, respectively. After confirmation of L. tropica isolates by polymerase chain reaction (PCR), the recombinant plasmid pcDNA-rPTR (antisense) was transfected via electroporation and cultured on M199. Isolates in form of promastigotes were treated with different concentrations of MA and read using an enzyme-linked immunosorbent assay (ELISA) reader and the half inhibitory concentration (IC All three transfected isolates displayed a reduction in optical density compared with the promastigotes in respective isolates, although there was no significant difference between non-healing and healing isolates. In contrast, in the clinical form (amastigotes), there was a significant difference between non-healing and healing isolates (p < 0.05). The results indicated that the PTR1 gene reduced the efficacy of the drug, and its inhibition by antisense and could improve the treatment of non-healing cases. These findings have future implications in the prophylactic and therapeutic modality of non- healing Leishmania isolates to drug.
Sections du résumé
BACKGROUND
BACKGROUND
Drug resistance is a common phenomenon frequently observed in countries where leishmaniasis is endemic. Due to the production of the pteridine reductase enzyme (PTR1), drugs lose their efficacy, and consequently, the patient becomes unresponsive to treatment. This study aimed to compare the in vitro effect of meglumine antimoniate (MA) on non- healing Leishmania tropica isolates and on MA transfected non-healing one to PTR1.
METHODS
METHODS
Two non-healing and one healing isolates of L. tropica were collected from patients who received two courses or one cycle of intralesional MA along with biweekly liquid nitrogen cryotherapy or systemic treatment alone, respectively. After confirmation of L. tropica isolates by polymerase chain reaction (PCR), the recombinant plasmid pcDNA-rPTR (antisense) was transfected via electroporation and cultured on M199. Isolates in form of promastigotes were treated with different concentrations of MA and read using an enzyme-linked immunosorbent assay (ELISA) reader and the half inhibitory concentration (IC
RESULTS
RESULTS
All three transfected isolates displayed a reduction in optical density compared with the promastigotes in respective isolates, although there was no significant difference between non-healing and healing isolates. In contrast, in the clinical form (amastigotes), there was a significant difference between non-healing and healing isolates (p < 0.05).
CONCLUSION
CONCLUSIONS
The results indicated that the PTR1 gene reduced the efficacy of the drug, and its inhibition by antisense and could improve the treatment of non-healing cases. These findings have future implications in the prophylactic and therapeutic modality of non- healing Leishmania isolates to drug.
Identifiants
pubmed: 33283321
doi: 10.1002/jcla.23670
pmc: PMC7957997
doi:
Substances chimiques
Antiprotozoal Agents
0
DNA, Antisense
0
Protozoan Proteins
0
Meglumine Antimoniate
75G4TW236W
Oxidoreductases
EC 1.-
pteridine reductase
EC 1.1.1.33
Banques de données
GENBANK
['EF113119']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23670Subventions
Organisme : Vice Chancellor for Research of Kerman University of Medical Sciences
ID : 9010605468
Informations de copyright
© 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.
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