Genomic Insights into the Phosphatidylinositol-Specific Phospholipase C Gene Family in Leishmania major and Leishmania infantum: Expression Patterns and Potential Association with Drug Resistance

TL;DR

This study explores PI-PLC genes in Leishmania species and finds they may be linked to drug resistance, offering potential for new diagnostic tools.

Contribution

The study identifies and characterizes PI-PLC genes in Leishmania species and links their expression to drug resistance for the first time.

Findings

Twenty-two PI-PLC genes were identified in each species with conserved domains and diverse biochemical traits.

Differential expression of PI-PLC genes was observed in antimony-resistant Leishmania strains.

PI-PLC genes may serve as molecular markers for drug resistance in Leishmania.

Abstract

Background/Objectives: Timely and effective clinical management of leishmaniasis depends on a deep understanding of parasite biology and drug resistance mechanisms. Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes are critical for parasite survival and immune evasion and possibly influence treatment outcomes. This study aimed to characterize the PI-PLC gene family in the Leishmania infantum and Leishmania major genomes, with a focus on their expression profiles in antimony-susceptible and -resistant strains to uncover their diagnostic and prognostic relevance. Methods: This study conducted a comprehensive genome-wide screening to identify PI-PLC genes in L. infantum and L. major, followed by detailed analyses of their gene structures, conserved motifs, chromosomal localization, and phylogenetic relationships. To explore potential roles in drug resistance and clinical prognosis, RNA-seq data from antimony-resistant and -susceptible L. infantum strains were analyzed for differential gene expression. Results: Twenty-two PI-PLC genes were identified in each species, displaying conserved catalytic domains and diverse biochemical characteristics. Phylogenetic and chromosomal analyses revealed gene clustering and distribution patterns. Importantly, expression profiling highlighted several PI-PLC genes with differential regulation in resistant strains, suggesting a role in treatment response and potential as molecular markers. Conclusions: Our findings suggest that PI-PLC genes may be associated with drug susceptibility in L. infantum, warranting further functional investigation to validate their role as potential molecular markers.

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