ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells

In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes....

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2015-08, Vol.10 (8), p.e0134779
Main Authors: Lara, Flavio Alves, Pohl, Paula C, Gandara, Ana Caroline, Ferreira, Jessica da Silva, Nascimento-Silva, Maria Clara, Bechara, Gervásio Henrique, Sorgine, Marcos H F, Almeida, Igor C, Vaz, Jr, Itabajara da Silva, Oliveira, Pedro L
Format: Article
Language:English
Subjects:
ABC transporter
ABC transporters
Acaricides
Acaricides - chemistry
Adenosine Triphosphate - chemistry
Analogs
Animals
Antibodies - chemistry
Arachnids
Arthropod Proteins - chemistry
ATP
ATP-Binding Cassette Transporters - chemistry
Binding
Biology
Blood
Cattle
Chemical properties
Chromatography, High Pressure Liquid
Cyclosporine - chemistry
Cyclosporins
Detoxification
Digestion
Drug resistance
Enzymes
Female
Fluorescent indicators
Heme
Heme - chemistry
Hemoglobin
Hemoglobins
Intestines - physiology
Membranes
Metalloporphyrins - chemistry
Metalloporphyrins - pharmacokinetics
Midgut
Molecular chains
Parasitic diseases
Pesticide resistance
Pesticides
Physiological aspects
Protein Binding
Protein Structure, Tertiary
Proteolysis
Protoporphyrins - chemistry
Rhipicephalus - physiology
Rhipicephalus microplus
Rhodamine
Rhodamine 123 - chemistry
Rhodamine 123 - pharmacokinetics
RNA Interference
RNA-mediated interference
Substrates
Tick Infestations - drug therapy
Ticks
Toluidines - chemistry
Toluidines - pharmacokinetics
Toxicity
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a well-known inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new molecular mechanism of resistance to pesticides.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0134779