Leishmania (V.) guyanensis: isolation and characterization of glucantime-resistant cell lines.
A glucantime sensitive Leishmania (V.) guyanensis strain was used to obtain in vitro resistant cell lines, by increments in glucantime concentrations employing both one step and stepwise protocols. Whereas the effective concentration of drug that inhibited the growth of wild type cells by 50% (EC50 value) was 0.20 mg Sb(v)/mL, the resistant cells were able to grow in glucantime concentrations greater than 8.0 mg/mL. The resistant cell lines were partially characterized by their in vitro response to glucantime, the stability of resistance phenotype, cross resistance to a range of drugs, and also by the analysis of total DNA fragments generated by restriction endonucleases and blot hybridization. Amplified DNA sequence similar to a P-glycoprotein analog from Leishmania tarentolae (ltpgpA gene) was observed in all the resistant cell lines obtained through the one-step protocol. These cell lines showed cross resistance to heavy metals but were sensitive to puromycin, vinblastine, and pentostam.
Ferreira-Pinto
K C
KC
Departamento de Microbiologia, Instituto de Ciências Biologicas, Universidade Federal de Minas Gerais, Brasil.
Miranda-Vilela
A L
AL
Anacleto
C
C
Fernandes
A P
AP
Abdo
M C
MC
Petrillo-Peixoto
M L
ML
Moreira
E S
ES
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D000965:Antimony / Q000494:pharmacology; D000966:Antimony Potassium Tartrate / Q000494:pharmacology; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001149:Arsenates / Q000494:pharmacology; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D018628:Gene Dosage; D017125:Genes, Protozoan; D007891:Leishmania / Q000235:genetics; D018334:Leishmania guyanensis / Q000187:drug effects* / Q000235:genetics; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology*; D010087:Oxides / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000981:Antiprotozoal Agents; D001149:Arsenates; D016054:DNA, Protozoan; D009942:Organometallic Compounds; D010087:Oxides; C091696:antimony oxide; D011691:Puromycin; D014747:Vinblastine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony; D000966:Antimony Potassium Tartrate; C025657:arsenic acid; D000967:Antimony Sodium Gluconate