Academic Journal
Antifungal repurposing of clinical chelator DMSA against Cryptococcus neoformans via laccase and histidine biosynthesis inhibition.
| Title: | Antifungal repurposing of clinical chelator DMSA against Cryptococcus neoformans via laccase and histidine biosynthesis inhibition. |
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| Authors: | Zhang C; Department of Dermatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Peng M; Department of Dermatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Hu Q; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China., Huang S; State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China., Zhang Q; Jinling Clinical Medical College, Nanjing Medical University, China., Zhu J; State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China., Sang H; Department of Dermatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: sanghong@nju.edu.cn., Kong Q; Department of Dermatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: kongqingtao2008@163.com. |
| Source: | Microbial pathogenesis [Microb Pathog] 2026 May; Vol. 214, pp. 108375. Date of Electronic Publication: 2026 Feb 10. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Academic Press Country of Publication: England NLM ID: 8606191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-1208 (Electronic) Linking ISSN: 08824010 NLM ISO Abbreviation: Microb Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; Orlando : Academic Press, c1986- |
| MeSH Terms: | Cryptococcus neoformans*/drug effects , Cryptococcus neoformans*/enzymology , Cryptococcus neoformans*/pathogenicity , Laccase*/antagonists & inhibitors , Laccase*/metabolism , Laccase*/drug effects , Antifungal Agents*/pharmacology , Chelating Agents*/pharmacology , Histidine*/biosynthesis , Histidine*/antagonists & inhibitors , Succimer*/pharmacology , Drug Repositioning*, Biofilms/drug effects ; Biofilms/growth & development ; Cryptococcosis/microbiology ; Cryptococcosis/drug therapy ; Moths/microbiology ; Urease/metabolism ; Fungal Capsules/drug effects ; Animals ; Microbial Sensitivity Tests ; Virulence Factors ; Humans ; Disease Models, Animal |
| Abstract: | As a globally distributed opportunistic fungus, Cryptococcus neoformans poses a significant threat to human health by causing fatal meningitis, which is associated with high mortality and morbidity rates. Current antifungals-polyenes, flucytosine, and azoles-are limited by toxicity and resistance, underscoring the need for new agents. This study evaluated dimercaptosuccinic acid (DMSA), a chelating agent used in the treatment of heavy metal poisoning, beginning with its effect on the virulence factor laccase. DMSA showed broad-spectrum activity against standard (H99, B3501) and clinical isolate strains, with MIC values of 32-64 μg/mL. It inhibited laccase (IC (Copyright © 2026. Published by Elsevier Ltd.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cryptococcus neoformans; Dimercaptosuccinic acid; Drug repurposing; Histidine biosynthesis; Laccase |
| Substance Nomenclature: | EC 1.10.3.2 (Laccase) 0 (Antifungal Agents) 0 (Chelating Agents) 4QD397987E (Histidine) DX1U2629QE (Succimer) 0 (Virulence Factors) EC 3.5.1.5 (Urease) |
| Entry Date(s): | Date Created: 20260212 Date Completed: 20260707 Latest Revision: 20260707 |
| Update Code: | 20260708 |
| DOI: | 10.1016/j.micpath.2026.108375 |
| PMID: | 41679612 |
| Database: | MEDLINE |
| ISSN: | 1096-1208 |
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| DOI: | 10.1016/j.micpath.2026.108375 |