Variability and variation in drug susceptibility among Giardia duodenalis isolates and clones exposed to 5-nitroimidazoles and benzimidazoles in vitro.
OBJECTIVE
We analysed, in a cell-by-cell study, the in vitro susceptibility of Giardia duodenalis strains, including Mexican isolates and their clones to 5-nitroimidazoles and benzimidazoles.


METHODS
Fluorogenic dye staining (FDA-PI) and cell morphology (CM) assays, two fast and direct techniques, replaced the indirect 'gold standard' method (subculture in liquid medium) in the evaluation of 5-nitroimidazoles and benzimidazoles, respectively.


RESULTS
Under these conditions, the activity of several 5-nitroimidazole and benzimidazole derivatives was consistent with their known efficacy, but parasite stocks exhibited a greater variability in response to 5-nitroimidazoles compared with benzimidazoles. Also, consecutive progenies from single stocks maintained in continuous subculture in drug-free media displayed changes (variations) in the proportions of drug resistant (R/T) subpopulations when exposed to sublethal concentrations of 5-nitroimidazoles and benzimidazoles. These were again more variable upon exposure to 5-nitroimidazoles than to benzimidazoles. Variations were not due to drug susceptibility shifts in parent trophozoites since analysis of cytokinetic processes showed a predominant pattern of susceptible/susceptible or resistant/resistant daughters, whereas susceptible/resistant daughters were scarce.


CONCLUSIONS
Our observations support the idea that G. duodenalis cultures exhibit variations in their response to 5-nitroimidazoles and benzimidazoles as a result of a drug-independent competition between drug-susceptible and drug-resistant subpopulations when parasites are subcultured.
Argüello-García
Raúl
R
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados-IPN, Apartado Postal 14-740 07360 México, DF, México.
Cruz-Soto
Maricela
M
Romero-Montoya
Lydia
L
Ortega-Pierres
Guadalupe
G
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D005872:Giardia / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D005873:Giardiasis / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D009593:Nitroimidazoles / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D009593:Nitroimidazoles; C052587:4-nitroimidazole