Genomic Characterization of a Locally Transmitted Leishmania mexicana Isolate from Texas

Cutaneous leishmaniasis (CL) is caused by Leishmania species transmitted by sand flies. Although considered a neglected tropical disease, growing evidence indicates that local transmission can occur in subtropical, higher-resource regions where sand fly vectors are present, including the southern United States. Here, we report the first whole-genome sequence of Leishmania mexicana from an autochthonous U.S. case--a 3-year-old boy from Ellis County, Texas, with no travel history. Genomic DNA was extracted from a skin biopsy specimen and sequenced using Illumina technology. Phylogenomic analysis based on nuclear and mitochondrial SNPs confirmed the isolate as L. mexicana, clustering with other members of the L. mexicana complex. The parasite exhibited a predominantly disomic karyotype, with chromosome 30 displaying trisomy. We identified 172 genes with significant copy number variations, including genes involved in ubiquitination, nucleic acid metabolism, and protein translation. Additionally, 53,964 SNPs were detected, over 22,000 of which were predicted to have moderate or high functional impact, affecting genes linked to host-pathogen interactions, metabolic pathways, and signal transduction. This study provides the first genomic characterization of a locally acquired L. mexicana strain in the U.S. and underscores the value of molecular surveillance and increased clinical awareness of leishmaniasis in subtropical regions where competent vectors are present.