Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum
Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for p...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-08-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320716300070 |
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| author | Verónica Gómez Pérez Raquel García-Hernandez Victoriano Corpas-López Ana M. Tomás Joaquina Martín-Sanchez Santiago Castanys Francisco Gamarro |
| author_facet | Verónica Gómez Pérez Raquel García-Hernandez Victoriano Corpas-López Ana M. Tomás Joaquina Martín-Sanchez Santiago Castanys Francisco Gamarro |
| author_sort | Verónica Gómez Pérez |
| collection | DOAJ |
| description | Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. We have studied the susceptibility profile to antimony and other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin) in Leishmania infantum isolates extracted from a dog before and after two therapeutic interventions with meglumine antimoniate (subcutaneous Glucantime®, 100 mg/kg/day for 28 days). After the therapeutic intervention, these parasites were significantly less susceptible to antimony than pretreatment isolate, presenting a resistance index of 6-fold to SbIII for promastigotes and >3-fold to SbIII and 3-fold to SbV for intracellular amastigotes. The susceptibility profile of this resistant L. infantum line is related to a decreased antimony uptake due to lower aquaglyceroporin-1 expression levels. Additionally, other mechanisms including an increase in thiols and overexpression of enzymes involved in thiol metabolism, such as ornithine decarboxylase, trypanothione reductase, mitochondrial tryparedoxin and mitochondrial tryparedoxin peroxidase, could contribute to the resistance as antimony detoxification mechanisms. A major contribution of this study in a canine L. infantum isolate is to find an antimony-resistant mechanism similar to that previously described in other human clinical isolates. |
| first_indexed | 2024-12-14T19:35:13Z |
| format | Article |
| id | doaj.art-804426a8f78a44c69810870a8bd33090 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-14T19:35:13Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-804426a8f78a44c69810870a8bd330902022-12-21T22:49:55ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072016-08-016213313910.1016/j.ijpddr.2016.04.003Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantumVerónica Gómez Pérez0Raquel García-Hernandez1Victoriano Corpas-López2Ana M. Tomás3Joaquina Martín-Sanchez4Santiago Castanys5Francisco Gamarro6Instituto de Parasitología y Biomedicina “López-Neyra”, CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Granada, SpainDepartamento de Parasitología, Facultad de Farmacia, Universidad de Granada, Granada, SpainIBMC – Institute for Molecular and Cell Biology, Porto, PortugalDepartamento de Parasitología, Facultad de Farmacia, Universidad de Granada, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Granada, SpainInstituto de Parasitología y Biomedicina “López-Neyra”, CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Granada, SpainVisceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. We have studied the susceptibility profile to antimony and other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin) in Leishmania infantum isolates extracted from a dog before and after two therapeutic interventions with meglumine antimoniate (subcutaneous Glucantime®, 100 mg/kg/day for 28 days). After the therapeutic intervention, these parasites were significantly less susceptible to antimony than pretreatment isolate, presenting a resistance index of 6-fold to SbIII for promastigotes and >3-fold to SbIII and 3-fold to SbV for intracellular amastigotes. The susceptibility profile of this resistant L. infantum line is related to a decreased antimony uptake due to lower aquaglyceroporin-1 expression levels. Additionally, other mechanisms including an increase in thiols and overexpression of enzymes involved in thiol metabolism, such as ornithine decarboxylase, trypanothione reductase, mitochondrial tryparedoxin and mitochondrial tryparedoxin peroxidase, could contribute to the resistance as antimony detoxification mechanisms. A major contribution of this study in a canine L. infantum isolate is to find an antimony-resistant mechanism similar to that previously described in other human clinical isolates.http://www.sciencedirect.com/science/article/pii/S2211320716300070LeishmaniaCanine leishmaniasisTherapeutic failureAntimony resistanceAntimony uptakeAquaglyceroporinThiolsPeroxiredoxins |
| spellingShingle | Verónica Gómez Pérez Raquel García-Hernandez Victoriano Corpas-López Ana M. Tomás Joaquina Martín-Sanchez Santiago Castanys Francisco Gamarro Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum International Journal for Parasitology: Drugs and Drug Resistance Leishmania Canine leishmaniasis Therapeutic failure Antimony resistance Antimony uptake Aquaglyceroporin Thiols Peroxiredoxins |
| title | Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum |
| title_full | Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum |
| title_fullStr | Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum |
| title_full_unstemmed | Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum |
| title_short | Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum |
| title_sort | decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of leishmania infantum |
| topic | Leishmania Canine leishmaniasis Therapeutic failure Antimony resistance Antimony uptake Aquaglyceroporin Thiols Peroxiredoxins |
| url | http://www.sciencedirect.com/science/article/pii/S2211320716300070 |
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