Role of the ABC Transporter PRP1 (ABCC7) in Pentamidine Resistance in
            <i>Leishmania</i>
            Amastigotes

Coelho, Adriano C.; Messier, Nadine; Ouellette, Marc; Cotrim, Paulo C.

doi:10.1128/aac.00404-07

Cited by 54 publications

(40 citation statements)

References 28 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The second ABC transporter involved in antimony resistance is ABCC7-PRP1 (12,17), a gene that is overexpressed in pentamidine-resistant Leishmania lines and confers significant cross-resistance to antimony (26). However, no clear association has been found between the amplification/overexpression of PRP1 and pentamidine resistance (27).…”

mentioning

confidence: 92%

A New ABC Half-Transporter in Leishmania major Is Involved in Resistance to Antimony

Manzano

García-Hernández

Castanys

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The characterization of ABCI4, a new intracellular ATP-binding cassette (ABC) half-transporter in Leishmania major, is described. We show that ABCI4 is involved in heavy metal export, thereby conferring resistance to Pentostam, to Sb(III), and to As(III) and Cd(II). Parasites overexpressing ABCI4 showed a lower mitochondrial toxic effect of antimony by decreasing reactive oxygen species production and maintained higher values of both the mitochondrial electrochemical potential and total ATP levels with respect to controls. The ABCI4 half-transporter forms homodimers as determined by a coimmunoprecipitation assay. A combination of subcellular localization studies under a confocal microscope and a surface biotinylation assay using parasites expressing green fluorescent protein-and FLAG-tagged ABCI4 suggests that the transporter presents a dual localization in both mitochondria and the plasma membrane. Parasites overexpressing ABCI4 present an increased replication in mouse peritoneal macrophages. We have determined that porphyrins are substrates for ABCI4. Consequently, the overexpression of ABCI4 confers resistance to some toxic porphyrins, such as zinc-protoporphyrin, due to the lower accumulation resulting from a significant efflux, as determined using the fluorescent zinc-mesoporphyrin, a validated heme analog. In addition, ABCI4 has a significant ability to efflux thiol after Sb(III) incubation, thus meaning that ABCI4 could be considered to be a potential thiol-X-pump that is able to recognize metal-conjugated thiols. In summary, we have shown that this new ABC transporter is involved in drug sensitivity to antimony and other compounds by efflux as conjugated thiol complexes.

show abstract

mentioning

confidence: 92%

A New ABC Half-Transporter in Leishmania major Is Involved in Resistance to Antimony

Manzano

García-Hernández

Castanys

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…15,18 This pump is effective for a diverse group of lipophilic compounds [15][16][17] and the higher the number of the Pgp 170 molecules on the cell membrane, the greater the ability of the isolate to expel the compound from its body. 14,18,[22][23][24] Our aim was to evaluate the MDR1 expression of Leishmania in Greece and Cyprus and present it geographically to assess the distribution of drug resistance and give the clinicians the knowledge required for effective treatment, which will safeguard against the expansion of this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15] The multidrug resistance (MDR1) gene expresses a transmembrane efflux pump (the P-glycoprotein molecule, Pgp 170 [16][17][18] ), which appears to play a key role in the phenomenon of drug resistance. 15,18 Control of the disease relies principally on chemotherapy, both in patients and dogs, 19 and antimony has been the main drug to combat the disease in the last 65 years.…”

Section: Introductionmentioning

confidence: 99%

Geographical Distribution of MDR1 Expression in Leishmania Isolates, from Greece and Cyprus, Measured by the Rhodamine-123 Efflux Potential of the Isolates, Using Flow Cytometry

Tsirigotakis

Christodoulou

Ntais

et al. 2016

The American Journal of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Leishmaniasis, a neglected vector-borne disease caused by the protozoan parasite Leishmania, is encountered in 98 countries causing serious concerns to public health. The most alarming is the development of parasite drug resistance, a phenomenon increasingly encountered in the field rendering chemotherapy ineffective. Although resistance to drugs is a complex phenomenon, the rate of efflux of the fluorescent dye Rhodamine-123 from the parasite body, using flow cytometry, is an indication of the isolate's ability to efflux the drug, thus avoiding death. The rate of efflux measured 275 Leishmania strains, isolated from patients and dogs from Greece and Cyprus, was measured and mapped to study the geographical distribution of the multidrug resistance (MDR) gene expression as an indication of the drug resistance of the parasite. The map showed that out of the seven prefectures, where dogs presented high efflux rates, five also had patients with high efflux rates. In one, out of the 59 prefectures studied, the highest number of isolates with efflux slope α > 1, in both human and dog isolates, was found; a fact which may suggest that spread of drug resistance is taking place. The virulence of the Leishmania strains, assessed after infecting human macrophages of the THP-1 cell line, fluctuated from 1% to 59.3% with only 2.5% of the isolates showing infectivity > 50%. The most virulent strains were isolated from Attica and Crete.

show abstract

“…Este gene codifica o transportador de membrana PRP1 (Pentamidine Resistance Protein), da superfamília de transportadores ABC (ATP Binding Cassette), e é capaz de conferir resistência a pentamidina às células selvagem do parasita após trasnfecção e super expressão gênica (Coelho et al, 2003;Coelho et al, 2006;Coelho et al, 2007).…”

Section: 2unclassified

“…Dados obtidos por microarray de DNA têm demonstrado que parasitos resistentes a drogas em diferentes espécies de Leishmania, podem apresentar genes super expressos envolvidos na resistência ao Sb(III) e ao MTX, mas que não estão descritos como genes relacionados com a amplificação gênica (Guimond et al, 2003;El Fadili et al, 2005;Marquis et al, 2005 (Coelho et al, 2007;Coelho et al, 2008). (Roberts et al, 2003).…”

Section: 2unclassified

Identificação e caracterização cromossomal de 9 loci de Leishmania (L.) major relacionados com resistência a inibidores da via de biossíntese do ergosterol

Camizotti¹

View full text Add to dashboard Cite

Role of the ABC Transporter PRP1 (ABCC7) in Pentamidine Resistance in Leishmania Amastigotes

Cited by 54 publications

References 28 publications

A New ABC Half-Transporter in Leishmania major Is Involved in Resistance to Antimony

A New ABC Half-Transporter in Leishmania major Is Involved in Resistance to Antimony

Geographical Distribution of MDR1 Expression in Leishmania Isolates, from Greece and Cyprus, Measured by the Rhodamine-123 Efflux Potential of the Isolates, Using Flow Cytometry

Identificação e caracterização cromossomal de 9 loci de Leishmania (L.) major relacionados com resistência a inibidores da via de biossíntese do ergosterol

Contact Info

Product

Resources

About