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.

AMB Express
|June 17, 2022
PubMed

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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