Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
PLoS Negl Trop Dis
; 7(10): e2481, 2013.
Article
in En
| MEDLINE
| ID: mdl-24147167
ABSTRACT
BACKGROUND:
Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V.) braziliensis. METHODOLOGY/PRINCIPALFINDINGS:
In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V.) braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.CONCLUSIONS:
Iron chelation leads to a multifactorial response that results in cellular collapse, starting with the interruption of cell proliferation and culminating in marked mitochondrial impairment in some parasites and their subsequent cell death, whereas others may survive and resume proliferating.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leishmania braziliensis
/
2,2'-Dipyridyl
/
Chelating Agents
/
Iron
/
Mitochondria
Limits:
Humans
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
PLoS Negl Trop Dis
Journal subject:
MEDICINA TROPICAL
Year:
2013
Document type:
Article
Affiliation country:
Brazil
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA