Drug resistance and P-glycoprotein gene amplification in the protozoan parasite Leishmania

1991 ◽  
Vol 142 (6) ◽  
pp. 737-746 ◽  
Author(s):  
M. Ouellette ◽  
P. Borst
1989 ◽  
Vol 7 (8) ◽  
pp. 1129-1136 ◽  
Author(s):  
D E Merkel ◽  
S A Fuqua ◽  
A K Tandon ◽  
S M Hill ◽  
A U Buzdar ◽  
...  

Multiple drug resistance (MDR), consisting of acquired cross resistance to anthracyclines, vinca alkyloids, and other antineoplastic antibiotics, has been described in a variety of cell lines. This MDR phenotype is associated with overexpression and sometimes amplification of a gene coding for a 170 kDa glycoprotein, termed P-glycoprotein. To understand the role of this mechanism in clinical breast cancer, 248 breast cancer specimens representing both untreated primary and refractory relapsing disease were probed for evidence of P-glycoprotein gene amplification or overexpression using Southern, Northern, or Western blot techniques. In no case was an increase in P-glycoprotein gene copy number or expression detected. Though these findings do not necessarily rule out a role for P-glycoprotein in mediating drug resistance in breast cancer, electrophoretic analysis of clinical specimens is unlikely to provide useful predictive information. More sensitive assays must be developed to overcome the difficulties inherent in analyzing heterogenous tissue samples.


2008 ◽  
Vol 52 (10) ◽  
pp. 3573-3579 ◽  
Author(s):  
Esther Castanys-Muñoz ◽  
José María Pérez-Victoria ◽  
Francisco Gamarro ◽  
Santiago Castanys

ABSTRACT Leishmaniasis treatment is hampered by the increased appearance of treatment failure. ATP-binding cassette (ABC) transporters are usually involved in drug resistance both in tumor cells and in microorganisms. Here we report the characterization of an ABCG-like transporter, LiABCG6, localized mainly at the plasma membrane in Leishmania protozoan parasites. When overexpressed, this half-transporter confers significant resistance to the leishmanicidal agents miltefosine and sitamaquine. This resistance phenotype is mediated by a reduction in intracellular drug accumulation. LiABCG6 also reduces the accumulation of short-chain fluorescent phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. As a whole, these results suggest that LiABCG6 could be implicated in phospholipid trafficking and drug resistance.


1989 ◽  
Vol 59 (5) ◽  
pp. 682-685 ◽  
Author(s):  
G Capranico ◽  
P De Isabella ◽  
C Castelli ◽  
R Supino ◽  
G Parmiani ◽  
...  

1991 ◽  
Vol 10 (4) ◽  
pp. 1009-1016 ◽  
Author(s):  
M. Ouellette ◽  
E. Hettema ◽  
D. Wüst ◽  
F. Fase-Fowler ◽  
P. Borst

1997 ◽  
Vol 96 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Ti Lin ◽  
Jeffrey M Trent ◽  
Dina Milliken ◽  
David S Shimm ◽  
Robert Donaldson ◽  
...  

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
E Xingi ◽  
D Smirlis ◽  
S Bisti ◽  
V Myrianthopoulos ◽  
P Magiatis ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 523
Author(s):  
Marianne Lebbad ◽  
Jadwiga Winiecka-Krusnell ◽  
Christen Rune Stensvold ◽  
Jessica Beser

The intestinal protozoan parasite Cryptosporidium is an important cause of diarrheal disease worldwide. The aim of this study was to expand the knowledge on the molecular epidemiology of human cryptosporidiosis in Sweden to better understand transmission patterns and potential zoonotic sources. Cryptosporidium-positive fecal samples were collected between January 2013 and December 2014 from 12 regional clinical microbiology laboratories in Sweden. Species and subtype determination was achieved using small subunit ribosomal RNA and 60 kDa glycoprotein gene analysis. Samples were available for 398 patients, of whom 250 (63%) and 138 (35%) had acquired the infection in Sweden and abroad, respectively. Species identification was successful for 95% (379/398) of the samples, revealing 12 species/genotypes: Cryptosporidium parvum (n = 299), C. hominis (n = 49), C. meleagridis (n = 8), C. cuniculus (n = 5), Cryptosporidium chipmunk genotype I (n = 5), C. felis (n = 4), C. erinacei (n = 2), C. ubiquitum (n = 2), and one each of C. suis, C. viatorum, C. ditrichi, and Cryptosporidium horse genotype. One patient was co-infected with C. parvum and C. hominis. Subtyping was successful for all species/genotypes, except for C. ditrichi, and revealed large diversity, with 29 subtype families (including 4 novel ones: C. parvum IIr, IIs, IIt, and Cryptosporidium horse genotype VIc) and 81 different subtypes. The most common subtype families were IIa (n = 164) and IId (n = 118) for C. parvum and Ib (n = 26) and Ia (n = 12) for C. hominis. Infections caused by the zoonotic C. parvum subtype families IIa and IId dominated both in patients infected in Sweden and abroad, while most C. hominis cases were travel-related. Infections caused by non-hominis and non-parvum species were quite common (8%) and equally represented in cases infected in Sweden and abroad.


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