Análise genômico comparativa de Leishmania Infantum: implicações da aneuploidia em mosaico na resistência a fármacos

Abstract

Leishmania infantum stands out for its remarkable genomic plasticity, which enables rapid adaptation to various selective pressures, including those imposed by drug therapies. Copy number variations (CNVs) have been associated with resistance phenotypes, directly impacting the parasite’s response to available treatments. Therefore, understanding the genomic mechanisms underlying resistance is essential for developing more effective therapeutic strategies. To characterize genomic content alterations in Leishmania infantum associated with different phenotypes, with emphasis on copy number variations and their functional impacts.This is an exploratory study with a quantitative approach, based on secondary data from public genomic sequencing. A total of 435 paired-end libraries were selected from the Sequence Read Archive (SRA), with a minimum coverage of 30x. Analyses included genome alignment (BWA), ploidy estimation (Samtools), calculation of median deviation, and application of the Mann-Whitney test to identify statistically significant genes (p < 0.001). The selected genes were subjected to functional enrichment analysis using the STRING platform. A total of 3,532 genes with statistically significant CNVs were identified, of which 70.5% were exclusive to the resistant group. The highest concentration of these variations was observed on chromosomes 12, 23, and 26. Functional analysis revealed a predominance of genes associated with metabolic processes and molecular functions critical to parasite survival. Furthermore, virulence factors such as GP63, HSP70, and OPB showed notable alterations in the resistant group. The data reinforce the central role of genomic plasticity in the adaptation of L. infantum, with gene amplification standing out as the main mechanism associated with drug resistance. The identification of CNVs and their functional implications provides valuable insights into virulence mechanisms and supports the development of new therapeutic approaches.