Impact of Genetic Diversity and Genome Plasticity of Leishmania spp. in Treatment and the Search for Novel Chemotherapeutic Targets.

Ana Maria Murta Santi,Silvane Maria Fonseca Murta

doi:10.3389/fcimb.2022.826287

Ana Maria Murta Santi, Silvane Maria Fonseca Murta

Open Access

https://doi.org/10.3389/fcimb.2022.826287

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Abstract

Leishmaniasis is one of the major public health concerns in Latin America, Africa, Asia, and Europe. The absence of vaccines for human use and the lack of effective vector control programs make chemotherapy the main strategy to control all forms of the disease. However, the high toxicity of available drugs, limited choice of therapeutic agents, and occurrence of drug-resistant parasite strains are the main challenges related to chemotherapy. Currently, only a small number of drugs are available for leishmaniasis treatment, including pentavalent antimonials (SbV), amphotericin B and its formulations, miltefosine, paromomycin sulphate, and pentamidine isethionate. In addition to drug toxicity, therapeutic failure of leishmaniasis is a serious concern. The occurrence of drug-resistant parasites is one of the causes of therapeutic failure and is closely related to the diversity of parasites in this genus. Owing to the enormous plasticity of the genome, resistance can occur by altering different metabolic pathways, demonstrating that resistance mechanisms are multifactorial and extremely complex. Genetic variability and genome plasticity cause not only the available drugs to have limitations, but also make the search for new drugs challenging. Here, we examined the biological characteristics of parasites that hinder drug discovery.

Highlights

Leishmaniases are a complex of diseases caused by different species of protozoan parasites of the genus Leishmania, which are transmitted to humans by the bite of infected female sand fly insects
Therapeutic failure in leishmaniasis is a growing problem and may be related to the Genetic Diversity of Drug-Resistant Leishmania occurrence of treatment-resistant parasites, and to other factors, such as patient immunity (Lopez-Velez et al, 1998; Alvar et al, 2008; Van Griensven et al, 2014); nutritional status, age, and gender of the patient (Dorlo et al, 2012; Ostyn et al, 2014); and whether the parasites are infected with any RNA viruses, such as LRV1 (Bourreau et al, 2015; Adaui et al, 2016)
We provide an overview of how genetic variation in the genus Leishmania influences the emergence of drug-resistant parasites, as well as the main tools for studying drug resistance mechanisms and searching for new drugs

Summary

Introduction

Leishmaniases are a complex of diseases caused by different species of protozoan parasites of the genus Leishmania, which are transmitted to humans by the bite of infected female sand fly insects. We provide an overview of how genetic variation in the genus Leishmania influences the emergence of drug-resistant parasites, as well as the main tools for studying drug resistance mechanisms and searching for new drugs.

Results

Conclusion