Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.

Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony has ge...

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Autores principales:	Ippokratis Messaritakis, Vasiliki Christodoulou, Apostolos Mazeris, Eleni Koutala, Antonia Vlahou, Sevasti Papadogiorgaki, Maria Antoniou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b82558e2b9a743869efcfa69fb3ac5e8
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spelling	oai:doaj.org-article:b82558e2b9a743869efcfa69fb3ac5e82021-11-18T07:42:22ZDrug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.1932-620310.1371/journal.pone.0065467https://doaj.org/article/b82558e2b9a743869efcfa69fb3ac5e82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776486/?tool=EBIhttps://doaj.org/toc/1932-6203Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. To test the hypothesis that drug efflux in Leishmania, as measured by flow cytometry using the fluorescent dye Rhodamine-123, is largely dependent on the number of efflux pumps an isolate can express, the amount of Pgp 170 molecules was assessed in ten field isolates (5 "resistant" and 5 "susceptible") using: Western Blotting, Confocal and Transmission Electron Microscopy, and proteomics. Their survival after exposure to three antileishmanial drugs, in vitro, was evaluated and clinical data were compared to the in vitro results. All isolates were resistant to Glucantime but susceptible to Miltefosine, whilst Amphotericin B was more effective on the "susceptible" isolates. The MDR gene, expressing the transmembrane efflux pump Pgp 170, appears to play a key role in the phenomenon of drug resistance. When "susceptible" versus "resistant" parasites were compared, it was shown that the higher the number of Pgp 170 molecules the higher the Rhodamine-123 efflux from the parasite body and, when exposed to the drug, the number of efflux pumps increased. However, the rate of this increase was not linear and it is possible that there is a maximum number of Pgp 170 molecules an isolate can express. Nevertheless, the phenomenon is a complex one and other factors and proteins are involved in which the HSP-70 group proteins, detected in the "resistant" isolates, may play a significant role.Ippokratis MessaritakisVasiliki ChristodoulouApostolos MazerisEleni KoutalaAntonia VlahouSevasti PapadogiorgakiMaria AntoniouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65467 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ippokratis Messaritakis Vasiliki Christodoulou Apostolos Mazeris Eleni Koutala Antonia Vlahou Sevasti Papadogiorgaki Maria Antoniou Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
description	Resistance of pathogens to drugs is a growing concern regarding many diseases. Parasites like Leishmania, Plasmodium and Entamoeba histolytica; and neoplastic cells, present the multidrug-resistant phenotype rendering chemotherapy ineffective. The acquired resistance of Leishmania to antimony has generated intense research on the mechanisms involved but the question has not yet been resolved. To test the hypothesis that drug efflux in Leishmania, as measured by flow cytometry using the fluorescent dye Rhodamine-123, is largely dependent on the number of efflux pumps an isolate can express, the amount of Pgp 170 molecules was assessed in ten field isolates (5 "resistant" and 5 "susceptible") using: Western Blotting, Confocal and Transmission Electron Microscopy, and proteomics. Their survival after exposure to three antileishmanial drugs, in vitro, was evaluated and clinical data were compared to the in vitro results. All isolates were resistant to Glucantime but susceptible to Miltefosine, whilst Amphotericin B was more effective on the "susceptible" isolates. The MDR gene, expressing the transmembrane efflux pump Pgp 170, appears to play a key role in the phenomenon of drug resistance. When "susceptible" versus "resistant" parasites were compared, it was shown that the higher the number of Pgp 170 molecules the higher the Rhodamine-123 efflux from the parasite body and, when exposed to the drug, the number of efflux pumps increased. However, the rate of this increase was not linear and it is possible that there is a maximum number of Pgp 170 molecules an isolate can express. Nevertheless, the phenomenon is a complex one and other factors and proteins are involved in which the HSP-70 group proteins, detected in the "resistant" isolates, may play a significant role.
format	article
author	Ippokratis Messaritakis Vasiliki Christodoulou Apostolos Mazeris Eleni Koutala Antonia Vlahou Sevasti Papadogiorgaki Maria Antoniou
author_facet	Ippokratis Messaritakis Vasiliki Christodoulou Apostolos Mazeris Eleni Koutala Antonia Vlahou Sevasti Papadogiorgaki Maria Antoniou
author_sort	Ippokratis Messaritakis
title	Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
title_short	Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
title_full	Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
title_fullStr	Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
title_full_unstemmed	Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.
title_sort	drug resistance in natural isolates of leishmania donovani s.l. promastigotes is dependent of pgp170 expression.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b82558e2b9a743869efcfa69fb3ac5e8
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Drug resistance in natural isolates of Leishmania donovani s.l. promastigotes is dependent of Pgp170 expression.

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