{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T06:09:18Z","timestamp":1778479758409,"version":"3.51.4"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    is the predominant etiological agent of visceral leishmaniasis (VL), whereas\n                    <jats:italic>Leishmania tropica<\/jats:italic>\n                    is classically associated with cutaneous leishmaniasis (CL). However, sporadic reports from Turkiye and other endemic settings indicate that\n                    <jats:italic>L. tropica<\/jats:italic>\n                    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\n                    <jats:italic>L. tropica<\/jats:italic>\n                    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\n                    <jats:italic>L. tropica<\/jats:italic>\n                    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\n                    <jats:italic>L. tropica<\/jats:italic>\n                    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\n                    <jats:italic>L. tropica<\/jats:italic>\n                    pathogenicity, and support the development of testable diagnostic and therapeutic targets. Collectively, the data challenge the prevailing view of\n                    <jats:italic>L. tropica<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1831849","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:29:29Z","timestamp":1778477369000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of viscerotropism-associated genes in Leishmania tropica strains causing visceral leishmaniasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Ahmet","family":"Ozbilgin","sequence":"first","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Celal Bayar University","place":["Manisa, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asl\u0131 Tetik","family":"Vardarl\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Ege University","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Cavus","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Celal Bayar University","place":["Manisa, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melike","family":"Dinc","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Izmir Institute of Technology","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varol","family":"Tunali","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, E\u015frefpa\u015fa Municipality Hospital","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Beyaz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Izmir Institute of Technology","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukran","family":"Kose","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Dokuz Eylul University","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talat","family":"Yalcin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Izmir Institute of Technology","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cumhur","family":"G\u00fcnd\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Ege University","place":["Izmir, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"106512","DOI":"10.1016\/J.ACTATROPICA.2022.106512","article-title":"Tissue tropism: is it an intrinsic characteristic of Leishmania species?","volume":"232","author":"Ait Maatallah","year":"2022","journal-title":"Acta Trop."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"435","DOI":"10.4269\/AJTMH.2008.79.435","article-title":"Isolation of Leishmania tropica from a patient with visceral leishmaniasis and disseminated cutaneous leishmaniasis, southern Iran","volume":"79","author":"Alborzi","year":"2008","journal-title":"Am. 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