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The role of ATP-binding cassette transporter genes expression in treatment failure cutaneous leishmaniasis
Mohammad Javad Boozhmehrani1,2, Gilda Eslami3, Ali Khamesipour4
1Department of Parasitology and Mycology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Abstract:
Leishmaniasis is one of the common diseases transmitted by sand flies in tropical and subtropical regions of the world. Currently, antimonial 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 no response to treatment. In this study, we evaluated ABCI4, ABCG2, ABCC7, ABCB4, and ABCC3 genes expression in Leishmania isolated from patients with non-healing cutaneous leishmaniasis and treatment response isolates. We selected 17 clinical isolates including 8 treatment failure and 9 treatment response samples from September 2020 to March 2021. The isolates were obtained from patients of Health Center Laboratory of Varzaneh, Isfahan, Iran with cutaneous leishmaniasis. The diagnosis was performed using microscopic observation. The samples were directly collected from the lesions. The expression profiling of genes was assessed using SYBR Green real-time PCR that was analyzed with delta-delta Ct. 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. 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 controversial over the mechanisms of treatment failure outcomes. In this study, we showed that ABC transporter genes could be considered one of the important mechanisms.
Insights
Investigating ATP-binding cassette (ABC) transporter genes in Leishmania revealed distinct expression patterns in treatment failure cases of cutaneous leishmaniasis. These ABC transporter genes are implicated as a key mechanism contributing to treatment failure in Leishmania infections.
Area of Science:
- Molecular Biology
- Parasitology
- Genetics
Background:
- Leishmaniasis is a sand fly-transmitted disease prevalent in tropical and subtropical areas.
- Antimonial derivatives are the primary treatment, but resistance is a growing concern.
- Certain ATP-binding cassette (ABC) transporter genes in Leishmania have been linked to treatment non-response.
Purpose of the Study:
- To evaluate the expression of specific ABC transporter genes (ABCI4, ABCG2, ABCC7, ABCB4, ABCC3) in Leishmania isolates from patients with treatment failure versus treatment response in cutaneous leishmaniasis.
- To elucidate the role of ABC transporter genes in the molecular mechanisms underlying treatment failure.
Main Methods:
- Analysis of 17 clinical Leishmania isolates (8 treatment failure, 9 treatment response) from cutaneous leishmaniasis patients in Iran.
- Gene expression profiling using SYBR Green real-time PCR and delta-delta Ct analysis.
- Microscopic observation for initial diagnosis and direct sample collection from skin lesions.
Main Results:
- All treatment failure isolates were identified as Leishmania major.
- Gene expression analysis demonstrated varied patterns of ABC transporter gene expression across different treatment failure isolates.
- The study suggests a significant role for ABC transporter genes in the observed treatment failures.
Conclusions:
- ATP-binding cassette (ABC) transporter genes exhibit differential expression patterns in Leishmania isolates associated with treatment failure in cutaneous leishmaniasis.
- These findings highlight ABC transporter genes as a potential crucial mechanism contributing to the challenge of treating Leishmania infections.
- Understanding these molecular mechanisms is vital for addressing treatment failure in cutaneous leishmaniasis globally.
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