scholarly journals The Role of ATP-binding Cassette Transporter Genes Expression for Treatment Failure in Cutaneous Leishmaniasis

2021 ◽  
Author(s):  
Mohammad Javad Boozhmehrani ◽  
Gilda Eslami ◽  
Ali Khamesipour ◽  
Abbas Ali Jafari ◽  
Mahmood Vakili
Keyword(s):  
Gene Expression ◽  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Abc Transporter ◽  
Molecular Mechanisms ◽  
Atp Binding ◽  
Genes Expression ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

Abstract Background: Leishmaniasis is one of the common diseases transmitted by sand flies in tropical and subtropical regions of the world. Currently, antimonal derivatives are the first line of treatment. Some of the members of the ATP-binding cassette (ABC) family of Leishmania are shown to be associated with resistance to antimonial. In this study, we evaluated ABCI4, ABCG2, ABCC7, and ABCC3 gene expression in Leishmania isolated from patients with non-healing cutaneous leishmaniasis. Results: Five cases were treatment failure that all of them were identified as L. major. All treatment failure clinical isolates were L. major. Gene expression analysis in treatment failure isolates showed that the ABC transported genes had a different pattern in each isolate. ABCC7 had overexpression in all isolates. Among the treatment failure isolates, only one sample had overexpression in all ABC transporter genes under study. Conclusions: Treatment failure has been reported for cutaneous leishmaniasis worldwide. Knowledge of the molecular mechanisms of treatment failure could solve this problem. ABC transporter genes are considered controversy over the mechanisms of treatment failure outcomes. In this study, we showed that ABC transporter genes could be considered one the important mechanisms.

scholarly journals Molecular characteristic of treatment failure clinical isolates of Leishmania major

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10969
Author(s):  
Gilda Eslami ◽  
Samira Hatefi ◽  
Vahid Ramezani ◽  
Masoud Tohidfar ◽  
Tatyana V. Churkina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phylogenetic Analysis ◽  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Active Form ◽  
Clinical Isolates ◽  
Molecular Characteristics ◽  
Atp Binding ◽  
Atp Binding Cassette

Background Leishmaniasis is a prevalent tropical disease caused by more than 20 Leishmania species (Protozoa, Kinetoplastida and Trypanosomatidae). Among different clinical forms of the disease, cutaneous leishmaniasis is the most common form, with an annual 0.6–1 million new cases reported worldwide. This disease’s standard treatment is pentavalent antimonial (SbV) that have been used successfully since the first half of the 20th century as a first-line drug. However, treatment failure is an increasing problem that is persistently reported from endemic areas. It is important to define and standardize tests for drug resistance in cutaneous leishmaniasis. SbV must be reduced to its trivalent active form (SbIII). This reduction occurs within the host macrophage, and the resultant SbIIIenters amastigotes via the aquaglyceroporin1 (AQP1) membrane carrier. Overexpression of AQP1 results in hypersensitivity of the parasites to SbIII, but resistant phenotypes accompany reduced expression, inactivation mutations, or deletion of AQP1. Hence, in this study, a phylogenetic analysis using barcode gene COXII and kDNA minicircle and expression analysis of AQP1 were performed in treatment failure isolates to assess the isolates’ molecular characteristics and to verify possible association with drug response. Methods Samples in this study were collected from patients with cutaneous leishmaniasis referred to the Diagnosis Laboratory Center in Isfahan Province, Iran, from October 2017 to December 2019. Among them, five isolates (code numbers 1–5) were categorized as treatment failures. The PCR amplification of barcode gene COXII and kDNA minicircle were done and subsequently analyzed using MEGA (10.0.5) to perform phylogenetics analysis of Treatment failures (TF) and Treatment response (TR) samples. Relative quantification of the AQP1 gene expression of TF and TR samples was assessed by real-time PCR. Results All samples were classified as L. major. No amplification failure was observed in the cases of barcode gene COXII and kDNA minicircle amplification. Having excluded the sequences with complete homology using maximum parsimony with the Bootstrap 500 method, four major groups were detected to perform phylogenetic analysis using COXII. The phylogenetic analysis using the barcode target of minicircle showed that all five treatment failure isolates were grouped in a separate sub-clade. Conclusions We concluded that the barcode gene COXII and the minicircle kDNA were suitable for identification, differentiation and phylogenetic analysis in treatment failure clinical isolates of Leishmania major. Also, AQP1 gene expression analyses showed that treatment failure isolates had less expression than TR isolates. The isolate with TF and overexpression of the AQP1 gene of other molecular mechanisms such as overexpression of ATP-binding cassette may be involved in the TR, such as overexpression of ATP-binding cassette which requires further research.

scholarly journals ATP-Binding Cassette (ABC) Transporter Genes Involved in Pyrethroid Resistance in the Malaria Vector Anopheles sinensis: Genome-Wide Identification, Characteristics, Phylogenetics, and Expression Profile

2019 ◽  
Vol 20 (6) ◽  
pp. 1409 ◽  
Author(s):  
Qiyi He ◽  
Zhentian Yan ◽  
Fengling Si ◽  
Yong Zhou ◽  
Wenbo Fu ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Pyrethroid Resistance ◽  
Expression Profiles ◽  
Anopheles Sinensis ◽  
Atp Binding ◽  
Rna Seq ◽  
Transporter Family ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

background: The ATP-binding cassette (ABC) transporters family is one of the largest families of membrane proteins existing in all living organisms. Pyrethroid resistance has become the largest unique obstacle for mosquito control worldwide. ABC transporters are thought to be associated with pyrethroid resistance in some agricultural pests, but little information is known for mosquitoes. Herein, we investigated the diversity, location, characteristics, phylogenetics, and evolution of ABC transporter family of genes in the Anopheles sinensis genome, and identified the ABC transporter genes associated with pyrethroid resistance through expression profiles using RNA-seq and qPCR. Results: 61 ABC transporter genes are identified and divided into eight subfamilies (ABCA-H), located on 22 different scaffolds. Phylogenetic and evolution analyses with ABC transporters of A. gambiae, Drosophila melanogaster, and Homo sapiens suggest that the ABCD, ABCG, and ABCH subfamilies are monophyly, and that the ABCC and ABCG subfamilies have experienced a gene duplication event. Both RNA-seq and qPCR analyses show that the AsABCG28 gene is uniquely significantly upregulated gene in all three field pyrethroid-resistant populations (Anhui, Chongqing, and Yunnan provinces) in comparison with a laboratory-susceptible strain from Jiangsu province. The AsABCG28 is significantly upregulated at 12-h and 24-h after deltamethrin exposure in three-day-old female adults. Conclusion: This study provides the information frame for ABC transporter subfamily of genes, and lays an important basis for the better understanding and further research of ABC transporter function in insecticide toxification. The AsABCG28 gene is associated with pyrethroid detoxification, and it functions at later period in the detoxification process for xenobiotics transportation.

scholarly journals Identification and Expression Characterization of ATP-Binding Cassette (ABC) Transporter Genes in Melon Fly

Insects ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 270
Author(s):  
Hui-Qian Xu ◽  
Meng Ma ◽  
Yun-Peng Ma ◽  
Su-Yun Zhang ◽  
Wei-Jun Li ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Lipid Membranes ◽  
Developmental Stages ◽  
Fat Body ◽  
Transmembrane Protein ◽  
Insect Pest ◽  
Atp Binding ◽  
Specific Substrate ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

The ATP-binding cassette (ABC) transporter is a protein superfamily that transports specific substrate molecules across lipid membranes in all living species. In insects, ABC transporter is one of the major transmembrane protein families involved in the development of xenobiotic resistance. Here, we report 49 ABC transporter genes divided into eight subfamilies (ABCA-ABCH), including seven ABCAs, seven ABCBs, 10 ABCCs, two ABCDs, one ABCE, three ABCFs, 16 ABCGs, and three ABCHs according to phylogenetic analysis in Zeugodacus cucurbitae, a highly destructive insect pest of cucurbitaceous and other related crops. The expressions level of 49 ABC transporters throughout various developmental stages and within different tissues were evaluated by quantitative transcriptomic analysis, and their expressions in response to three different insecticides were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). These ABC transporter genes were widely expressed at developmental stages but most highly expressed in tissues of the midgut, fat body and Malpighian tube. When challenged by exposure to three insecticides, abamectin, β-cypermethrin, and dinotefuran, the expressions of ZcABCB7 and ZcABCC2 were significantly up-regulated. ZcABCB1, ZcABCB6, ZcABCB7, ZcABCC2, ZcABCC3, ZcABCC4, ZcABCC5, and ZcABCC7 were significantly up-regulated in the fat body at 24 h after β-cypermethrin exposure. These data suggest that ZcABCB7 and ZcABCC2 might play key roles in xenobiotic metabolism in Z. cucurbitae. Collectively, these data provide a foundation for further analysis of ABCs in Z. cucurbitae.

Repeated Ivermectin Treatment Induces Ivermectin Resistance in Strongyloides ratti by Upregulating the Expression of ATP-Binding Cassette Transporter Genes

2021 ◽  
Author(s):  
Chatchawan Sengthong ◽  
Manachai Yingklang ◽  
Kitti Intuyod ◽  
Ornuma Haonon ◽  
Porntip Pinlaor ◽  
...  
Keyword(s):  
Larval Development ◽  
Abc Transporter ◽  
Resistance Mechanism ◽  
Atp Binding ◽  
Expression Levels ◽  
Atp Binding Cassette Transporter ◽  
Sensitivity Tests ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

Ivermectin (IVM) is a widely used anthelmintic. However, with widespread use comes the risk of the emergence of IVM resistance, particularly in strongyloidiasis. Adenosine triphosphate (ATP)-binding cassette (ABC) transporter genes play an important role in the IVM-resistance mechanism. Here, we aimed to establish an animal experimental model of IVM resistance by frequent treatment of Strongyloides ratti with subtherapeutic doses of IVM, resistance being evaluated by the expression levels of ABC transporter genes. Rats infected with S. ratti were placed in experimental groups as follows: 1) untreated control (control); 2) treated with the mutagen ethyl methanesulfonate (EMS); 3) injected with 100 µg/kg body weight of IVM (IVM); 4) treated with a combination of EMS and IVM (IVM+EMS). Parasites were evaluated after four generations. Extent of IVM resistance was assessed using IVM sensitivity, larval development, and expression of ABC genes. By the F4 generation, S. ratti in the IVM group exhibited significantly higher levels of IVM resistance than did other groups according to in vitro drug-sensitivity tests and inhibition of larval development (IC50 = 36.60 ng/mL; 95% CI: 31.6, 42.01). Expression levels of ABC isoform genes (ABCA, ABCF, and ABCG) were statistically significantly higher in the IVM-resistant line compared with the susceptible line. In conclusion, IVM subtherapeutic doses induced IVM resistance in S. ratti by the F4 generation with corresponding upregulation of some ABC isoform genes. The study provides a model for inducing and assessing drug resistance in Strongyloides.

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