Akademik Veri Yönetim Sistemi
FRONTIERS IN MICROBIOLOGY, cilt.17, ss.1-14, 2026 (SCI-Expanded, Scopus)
Leishmania infantum is the predominant etiological agent of visceral leishmaniasis (VL), whereas Leishmania tropica is classically associated with cutaneous leishmaniasis (CL). However, sporadic reports from Turkiye and other endemic settings indicate that L. tropica may also cause VL, suggesting that specific parasite determinants enable adaptation to visceral tissues. The molecular basis of this phenotypic shift remains insufficiently understood. This study aimed to define genetic factors associated with visceralization in L. tropica by integrating clinical isolates from patients with VL and CL and evaluating candidate genes involved in oxidative stress defense, mitochondrial function, proteolysis, and metabolic adaptation. Fourteen patients diagnosed between 2012 and 2022 were included, comprising seven VL and seven CL cases. Parasites isolated from clinical specimens were cultured and genotyped as L. tropica using real-time quantitative PCR targeting the internal transcribed spacer 1 region. Gene-expression profiling by qRT-PCR focused on Cytochrome C Oxidase subunit IV, Metallo-peptidase (Clan MA(E), Family M32), Oligopeptidase B, Peroxiredoxin 1, Peroxiredoxin 2, Pyruvate kinase, and Succinyl-CoA:3-ketoacid-coenzyme A transferase. Compared with CL isolates and reference strains, VL isolates demonstrated markedly increased mRNA expression of Peroxiredoxin 1 and Peroxiredoxin 2 and Cytochrome C Oxidase subunit IV, with approximately 17-fold and 21-fold elevations, respectively. Additional increases were observed in metallo-peptidase, Oligopeptidase B, and Succinyl-CoA:3-ketoacid-coenzyme A transferase, supporting a broader program of antioxidant, mitochondrial, proteolytic, and metabolic adaptation. Targeted next-generation sequencing identified multiple coding variants in Oligopeptidase B and the M32 metallo-peptidase, suggesting potential contributions to phenotypic divergence between VL and CL isolates. Viscerotropic L. tropica exhibits a distinct molecular profile characterized by enhanced antioxidant defense, mitochondrial activity, proteolytic capacity, and metabolic flexibility. These findings identify plausible genetic drivers of visceralization, expand current understanding of L. tropica pathogenicity, and support the development of testable diagnostic and therapeutic targets. Collectively, the data challenge the prevailing view of L. tropica as an exclusively cutaneous parasite. The results also provide a rational framework for future functional validation studies aimed at clarifying causality, refining biomarkers, and prioritizing parasite specific intervention strategies in endemic settings globally.