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In vitro activity of the anthelmintic drug niclosamide against Sporothrix spp. strains with distinct genetic and antifungal susceptibility backgrounds

  • Clinical Microbiology - Research Paper
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Abstract

The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.

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Data Availability

The authors declare that the data supporting the findings of this study are available within the paper. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request.

References

  1. Chakrabarti A, Bonifaz A, Gutierrez-Galhardo MC, Mochizuki T, Li S (2015) Global epidemiology of sporotrichosis. Med Mycol 53:3–14

    Article  CAS  PubMed  Google Scholar 

  2. Albuquerque PC, Fonseca E Fonseca B de P, Zicker F, Zancopé-Oliveira RM, Almeida-Paes R (2020) Bibliometric assessment and key messages of sporotrichosis research (1945–2018). F1000Res 9:654

  3. Orofino-Costa R, Freitas DFS, Bernardes-Engemann AR, Rodrigues AM, Talhari C, Ferraz CE, Veasey JV, Quintella L, Sousa MSLA, Vettorato R, Almeida-Paes R, de Macedo PM (2022) Human sporotrichosis: recommendations from the Brazilian Society of Dermatology for the clinical, diagnostic and therapeutic management. An Bras Dermatol 97:757–777

    Article  PubMed  PubMed Central  Google Scholar 

  4. World Health Organization (2023) Global report on neglected tropical disease. Available at https://www.who.int/teams/control-of-neglected-tropical-diseases/global-report-on-neglected-tropical-diseases-2023. Accessed 03/08/2024

  5. Carlos IZ, Sassá MF, da Graça Sgarbi DB, Placeres MCP, Maia DCG (2009) Current research on the immune response to experimental sporotrichosis. Mycopathologia 168:1–10

    Article  CAS  PubMed  Google Scholar 

  6. Bonifaz A, Tirado-Sánchez A (2017) Cutaneous disseminated and extracutaneous sporotrichosis: current status of a complex disease. J Fungi 3:6

    Article  Google Scholar 

  7. Poester VR, Basso RP, Stevens DA, Munhoz LS, Rabello VBS, Almeida-Paes R, Zancopé-Oliveira RM, Zanchi M, Benelli JL, Xavier MO (2022) Treatment of human sporotrichosis caused by Sporothrix brasiliensis. J Fungi 8:70

    Article  CAS  Google Scholar 

  8. Sharma B, Sharma AK, Sharma U (2022) Sporotrichosis: a comprehensive review on recent drug-based therapeutics and management. Curr Dermatol Rep 11:110–119

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bernardes-Engemann AR, Tomki GF, Rabello VBS, Almeida-Silva F, Freitas DFS, Gutierrez-Galhardo MC, Almeida-Paes R, Zancopé-Oliveira RM (2022) Sporotrichosis caused by non-wild type Sporothrix brasiliensis strains. Front Cell Infect Microbiol 12:893501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Almeida-Paes R, Oliveira MME, Freitas DFS, Valle ACF, Gutierrez-Galhardo MC, Zancopé-Oliveira RM (2017) Refractory sporotrichosis due to Sporothrix brasiliensis in humans appears to be unrelated to in vivo resistance. Med Mycol 55:507–517

    CAS  PubMed  Google Scholar 

  11. Borba-Santos LP, Rollin-Pinheiro R, da Silva FY, Dos Santos GMP, de Sousa Araújo GR, Rodrigues AM, Guimarães AJ, de Souza W, Frases S, Ferreira-Pereira A, Barreto-Bergter E, Rozental S (2022) Screening of pandemic response box library reveals the high activity of olorofim against pathogenic Sporothrix species. J Fungi 8:1004

    Article  CAS  Google Scholar 

  12. Dos Santos GMP, Borba-Santos LP, Vila T, Gremião IDF, Pereira SA, De Souza W, Rozental S (2022) Sporothrix spp. Biofilms impact in the zoonotic transmission route: feline claws associated biofilms, itraconazole tolerance, and potential repurposing for miltefosine. Pathogens 11:206

    Article  PubMed  PubMed Central  Google Scholar 

  13. Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A, Sanseau P, Cavalla D, Pirmohamed M (2019) Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18:41–58

    Article  CAS  PubMed  Google Scholar 

  14. Perfect JR (2017) The antifungal pipeline: a reality check. Nat Rev Drug Discov 16:603–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mittal N, Mittal R (2021) Repurposing old molecules for new indications: Defining pillars of success from lessons in the past European. J Pharmacol 912:174569

    CAS  Google Scholar 

  16. Poester VR, Hidalgo JED, Jardim LS, Trápaga MR, Rabello VBS, Almeida-Paes R, Zancope-Oliveira RM, Xavier MO (2023) Amlodipine and lufenuron as repurposing drugs against Sporothrix brasiliensis. PeerJ 11:e16443

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lim W, Verbon A, van de Sande W (2022) Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an open source drug discovery approach. Expert Opin Drug Discov 17:641–659

    Article  CAS  PubMed  Google Scholar 

  18. Borba-Santos LP, Gagini T, Ishida K, de Souza W, Rozental S (2015) Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole. J Med Microbiol 64:415–422

    Article  CAS  PubMed  Google Scholar 

  19. Poester VR, Munhoz LS, Stevens DA, Melo AM, Trápaga MR, Flores MM, Larwood DJ, Xavier MO (2023) Nikkomycin Z for the treatment of experimental sporotrichosis caused by Sporothrix brasiliensis. Mycoses 66:898–905

    Article  CAS  PubMed  Google Scholar 

  20. Weinbach EC, Garbus J (1969) Mechanism of action of reagents that uncouple oxidative phosphorylation. Nature 221:1016–1018

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Li Z, Brecher M, Deng Y-Q, Zhang J, Sakamuru S, Liu B, Huang R, Koetzner CA, Allen CA, Jones SA, Chen H, Zhang N-N, Tian M, Gao F, Lin Q, Banavali N, Zhou J, Boles N, Xia M, Kramer LD, Qin C-F, Li H (2017) Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Cell Res 27:1046–1064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li Y, Li P-K, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ (2014) Multi-targeted therapy of cancer by niclosamide: A new application for an old drug. Cancer Lett 349:8–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xu J, Shi P-Y, Li H, Zhou J (2020) Broad spectrum antiviral agent niclosamide and its therapeutic potential. ACS Infect Dis 6:909–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Almeida-Paes R, de Andrade IB, Ramos MLM, Rodrigues MVA, Nascimento VA, Bernardes-Engemann AR, Frases S (2021) Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi. Mem Inst Oswaldo Cruz 116:e210207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rodrigues AM, Gonçalves SS, de Carvalho JA, Borba-Santos LP, Rozental S, Camargo ZP (2022) Current progress on epidemiology, diagnosis, and treatment of sporotrichosis and their future trends. J Fungi 8:776

    Article  CAS  Google Scholar 

  26. Eudes Filho J, Santos IBD, Reis CMS, Patané JSL, Paredes V, Bernardes JPRA, Poggiani SDSC, Castro TCB, Gomez OM, Pereira SA, Schubach EYP, Gomes KP, Mavengere H, Alves LGB, Lucas J, Paes HC, Albuquerque P, Cruz LM, McEwen JG, Stajich JE, Almeida-Paes R, Zancopé-Oliveira RM, Matute DR, Barker BM, Felipe MSS, Teixeira MM, Nicola AM (2020) A novel Sporothrix brasiliensis genomic variant in Midwestern Brazil: evidence for an older and wider sporotrichosis epidemic. Emerg Microbes Infect 9:2515–2525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bellemare A, John T, Marqueteau S (2018) Fungal genomic DNA extraction methods for rapid genotyping and genome sequencing. Methods Mol Biol 1775:11–20

    Article  CAS  PubMed  Google Scholar 

  28. Rodrigues AM, de Hoog GS, Camargo ZP (2015) Molecular diagnosis of pathogenic Sporothrix species. PLoS Negl Trop Dis 9:e0004190

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rodrigues AM, Teixeira MM, De Hoog GS, Schubach TMP, Pereira SA, Fernandes GF, Lopes-Bezerra LM, Felipe MS, De Camargo ZP (2013) Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks. PLoS Negl Trop Dis 7:e2281

    Article  PubMed  PubMed Central  Google Scholar 

  30. Polzin T, Daneshmand SV (2003) On Steiner trees and minimum spanning trees in hypergraphs. Oper Res Lett 31:12–20

    Article  MathSciNet  Google Scholar 

  31. Clinical and Laboratory Standards Institute (2008) Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard - second edition. Clinical and Laboratory Standards Institute, Wayne, PA, USA

  32. Espinel-Ingroff A, Abreu DPB, Almeida-Paes R, Brilhante RSN, Chakrabarti A, Chowdhary A, Hagen F, Córdoba S, Gonzalez GM, Govender NP, Guarro J, Johnson EM, Kidd SE, Pereira SA, Rodrigues AM, Rozental S, Szeszs MW, Ballesté Alaniz R, Bonifaz A, Bonfietti LX, Borba-Santos LP, Capilla J, Colombo AL, Dolande M, Isla MG, Melhem MSC, Mesa-Arango AC, Oliveira MME, Panizo MM, Camargo ZP, Zancope-Oliveira RM, Meis JF, Turnidge J (2017) Multicenter, international study of MIC/MEC distributions for definition of epidemiological cutoff values for sporothrix species identified by molecular methods. Antimicrob Agents Chemother 6:e01057-e1117

    Google Scholar 

  33. Borba-Santos LP, Rodrigues AM, Gagini TB, Fernandes GF, Castro R, de Camargo ZP, Nucci M, Lopes-Bezerra LM, Ishida K, Rozental S (2015) Susceptibility of Sporothrix brasiliensis isolates to amphotericin B, azoles, and terbinafine. Med Mycol 53:178–188

    Article  CAS  PubMed  Google Scholar 

  34. Pfaller MA, Sheehan DJ, Rex JH (2004) Determination of fungicidal activities against yeasts and molds: lessons learned from bactericidal testing and the need for standardization. Clin Microbiol Rev 17:268–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. González-Pinzón R, Haggerty R, Myrold DD (2012) Measuring aerobic respiration in stream ecosystems using the resazurin-resorufin system. J Geophys Res 117:G00N06

  36. Coelho RA, Alves GM, Figueiredo-Carvalho MHG, Almeida-Silva F, de Souza GR, Lourenço MCS, Brito-Santos F, Amaral ACF, Almeida-Paes R (2022) New possibilities for chromoblastomycosis and phaeohyphomycosis treatment: identification of two compounds from the MMV Pathogen Box® that present synergism with itraconazole. Mem Inst Oswaldo Cruz 117:e220089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Odds FC (2003) Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52:1

    Article  CAS  PubMed  Google Scholar 

  38. Chen W, Mook RA, Premont RT, Wang J (2018) Niclosamide: beyond an antihelminthic drug. Cell Signal 41:89–96

    Article  CAS  PubMed  Google Scholar 

  39. Etchecopaz A, Toscanini MA, Gisbert A, Mas J, Scarpa M, Iovannitti CA, Bendezú K, Nusblat AD, Iachini R, Cuestas ML (2021) Sporothrix brasiliensis: A Review of an emerging south american fungal pathogen, its related disease, presentation and spread in Argentina. J Fungi 7:170

    Article  CAS  Google Scholar 

  40. Rachman R, Ligaj M, Chinthapalli S, Serafino-Wani R (2022) Zoonotic acquisition of cutaneous Sporothrix brasiliensis infection in the UK. BMJ Case Rep 15:e248418

    Article  PubMed  Google Scholar 

  41. Folliero V, Dell’Annunziata F, Roscetto E, Cammarota M, De Filippis A, Schiraldi C, Catania MR, Casolaro V, Perrella A, Galdiero M, Franci G (2022) Niclosamide as a repurposing drug against Corynebacterium striatum multidrug-resistant infections. Antibiotics 11:651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wei W, Liu H, Yuan J, Yao Y (2021) Targeting Wnt/β-catenin by anthelmintic drug niclosamide overcomes paclitaxel resistance in esophageal cancer. Fundam Clin Pharmacol 35:165–173

    Article  CAS  PubMed  Google Scholar 

  43. Teixeira MM, Rodrigues AM, Tsui CKM, Almeida LGP, Van Diepeningen AD, van den Ende BG, Fernandes GF, Kano R, Hamelin RC, Lopes-Bezerra LM, Vasconcelos ATR, de Hoog S, de Camargo ZP, Felipe MSS (2015) Asexual propagation of a virulent clone complex in a human and feline outbreak of sporotrichosis. Eukaryot Cell 14:158–169

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zhao L, Cui Y, Zhen Y, Yao L, Shi Y, Song Y, Chen R, Li S (2017) Genetic variation of Sporothrix globosa isolates from diverse geographic and clinical origins in China. Emerg Microbes Infect 6:e88

    Article  PubMed  PubMed Central  Google Scholar 

  45. Teixeira MM, Almeida-Paes R, Bernardes-Engemann AR, Nicola AM, de Macedo PM, Valle ACF, Gutierrez-Galhardo MC, Freitas DFS, Barker BM, Matute DR, Stajich JE, Zancopé-Oliveira RM (2022) Single nucleotide polymorphisms and chromosomal copy number variation may impact the Sporothrix brasiliensis antifungal susceptibility and sporotrichosis clinical outcomes. Fungal Genet Biol 163:103743

    Article  CAS  PubMed  Google Scholar 

  46. Cruz ILR, Freitas DFS, de Macedo PM, Gutierrez-Galhardo MC, Valle ACF, Almeida MA, Coelho RA, Brito-Santos F, Figueiredo-Carvalho MHG, Zancopé-Oliveira RM, Almeida-Paes R (2021) Evolution of virulence-related phenotypes of Sporothrix brasiliensis isolates from patients with chronic sporotrichosis and acquired immunodeficiency syndrome. Braz J Microbiol 52:5–18

    Article  CAS  PubMed  Google Scholar 

  47. Sanchotene KO, Brandolt TM, Klafke GB, Poester VR, Xavier MO (2017) In vitro susceptibility of Sporothrix brasiliensis: Comparison of yeast and mycelial phases. Med Mycol 55:869–876

    Article  CAS  PubMed  Google Scholar 

  48. Wong SSW, Samaranayake LP, Seneviratne CJ (2014) In pursuit of the ideal antifungal agent for Candida infections: high-throughput screening of small molecules. Drug Discov Today 19:1721–1730

    Article  CAS  PubMed  Google Scholar 

  49. Trilles L, Fernández-Torres B, Dos Santos LM, Wanke B, de Oliveira SA, Almeida-Paes R, Inza I, Guarro J (2005) In vitro antifungal susceptibilities of Sporothrix schenckii in two growth phases. Antimicrob Agents Chemother 49:3952–3954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fichman V, Almeida-Silva F, Freitas DFS, Zancopé-Oliveira RM, Gutierrez-Galhardo MC, Almeida-Paes R (2022) Severe Sporotrichosis caused by Sporothrix brasiliensis: Antifungal susceptibility and clinical outcomes. J Fungi 9:49

    Article  Google Scholar 

  51. Fichman V, Freitas DFS, Valle ACF, de Souza RV, Curi ALL, Valete-Rosalino CM, de Macedo PM, Varon AG, Figueiredo-Carvalho MHG, Almeida-Silva F, Zancopé-Oliveira RM, Oliveira RVC, Almeida-Paes R, Gutierrez-Galhardo MC (2022) Severe sporotrichosis treated with amphotericin B: A 20-year cohort study in an endemic area of zoonotic transmission. J Fungi 8:469

    Article  CAS  Google Scholar 

  52. Baes Pereira S, Dos Reis Gomes A, Bressan Waller S, Batista Xavier JR, Rodrigues AM, Kutscher Ripoll M, Ferreira MRA, Rochedo Conceição F, Osório de Faria R, Pascoti Bruhn FR (2022) Sporotrichosis in dogs: epidemiological and clinical-therapeutic profile and the emergence of itraconazole-resistant isolates. Med Mycol 60:myac089

    Article  PubMed  Google Scholar 

  53. Nakasu CCT, Waller SB, Ripoll MK, Ferreira MRA, Conceição FR, Gomes ADR, Osório LG, de Faria RO, Cleff MB (2021) Feline sporotrichosis: a case series of itraconazole-resistant Sporothrix brasiliensis infection. Braz J Microbiol 52:163–171

    Article  CAS  PubMed  Google Scholar 

  54. Waller SB, Dalla Lana DF, Quatrin PM, Ferreira MRA, Fuentefria AM, Mezzari A (2021) Antifungal resistance on Sporothrix species: an overview Braz. J Microbiol 52:73–80

    CAS  Google Scholar 

  55. Rodrigues AM, de Hoog GS, de Cássia PD, Brihante RSN, Sidrim JJC, Gadelha MF, Colombo AL, de Camargo ZP (2014) Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis. BMC Infect Dis 14:219

    Article  PubMed  PubMed Central  Google Scholar 

  56. de Carvalho JA, Beale MA, Hagen F, Mc F, Kano R, Bonifaz A, Toriello C, Negroni R, Rego RSM, Gremião IDF, Pereira SA, de Camargo ZP, Rodrigues AM (2021) Trends in the molecular epidemiology and population genetics of emerging Sporothrix species. Stud Mycol 100:100129

    PubMed  PubMed Central  Google Scholar 

  57. Abd Algaffar SO, Verbon A, van de Sande WWJ, Khalid SA (2021) Development and validation of an in vitro resazurin-based susceptibility assay against Madurella mycetomatis. Antimicrob Agents Chemother 65:e01338-e1420

    Article  PubMed  PubMed Central  Google Scholar 

  58. de Paula e Silva ACA, Oliveira HC, Silva JF, Sangalli-Leite F, Scorzoni L, Fusco-Almeida AM, Mendes-Giannini MJS (2013) Microplate alamarBlue assay for Paracoccidioides susceptibility testing. J Clin Microbiol 51:1250–1252

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wescott RB (1967) Efficacy of niclosamide in the treatment of Taenia taeniaeformis infections in cats. Am J Vet Res 28:1475–1477

    CAS  PubMed  Google Scholar 

  60. Gemmell MA, Johnstone PD, Oudemans G (1977) The effect of niclosamide on Echinococcus granulosus, Taenia hydatigena and Taenia ovis infections in dogs. Res Vet Sci 22:389–391

    Article  CAS  PubMed  Google Scholar 

  61. O’Neal SE, Pray IW, Vilchez P, Gamboa R, Muro C, Moyano LM, Ayvar V, Gavidia CM, Gilman RH, Gonzalez AE, Garcia HH, Cysticercosis Working Group in Peru (2021) Geographically targeted interventions versus mass drug administration to control Taenia solium Cysticercosis, Peru. Emerg Infect Dis 27:2389–2398

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rodriguez-Canul R, Fraser A, Allan JC, Dominguez-Alpizar JL, Argaez-Rodriguez F, Craig PS (1999) Epidemiological study of Taenia solium taeniasis/cysticercosis in a rural village in Yucatan state, Mexico. Ann Trop Med Parasitol 93:57–67

    CAS  PubMed  Google Scholar 

  63. Cairns DM, Boorgu DSSK, Levin M, Kaplan DL (2018) Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells. Biol Open 7:bio031807

    Article  PubMed  PubMed Central  Google Scholar 

  64. Lu T, Zheng X, Mao F, Cao Q, Cao Q, Zhu J, Li X, Lan L, Li B, Li J (2022) Novel niclosamide-derived adjuvants elevating the efficacy of polymyxin B against MDR Pseudomonas aeruginosa DK2. Eur J Med Chem 236:114318

    Article  CAS  PubMed  Google Scholar 

  65. Wieland A, Trageser D, Gogolok S, Reinartz R, Höfer H, Keller M, Leinhaas A, Schelle R, Normann S, Klaas L, Waha A, Koch P, Fimmers R, Pietsch T, Yachnis AT, Pincus DW, Steindler DA, Brüstle O, Simon M, Glas M, Scheffler B (2013) Anticancer effects of niclosamide in human glioblastoma. Clin Cancer Res 19:4124–4136

    Article  CAS  PubMed  Google Scholar 

  66. Andrews P, Thyssen J, Lorke D (1982) The biology and toxicology of molluscicides, Bayluscide. Pharmacol Ther 19:245–295

    Article  CAS  PubMed  Google Scholar 

  67. Jara MO, Warnken ZN, Sahakijpijarn S, Thakkar R, Kulkarni VR, Christensen DJ, Koleng JJ, Williams RO (2022) Oral delivery of niclosamide as an amorphous solid dispersion that generates amorphous nanoparticles during dissolution. Pharmaceutics 14:2568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Xie Y, Yao Y (2018) Octenylsuccinate hydroxypropyl phytoglycogen enhances the solubility and in-vitro antitumor efficacy of niclosamide. Int J Pharm 535:157–163

    Article  CAS  PubMed  Google Scholar 

  69. Mook RA, Wang J, Ren X-R, Chen M, Spasojevic I, Barak LS, Lyerly HK, Chen W (2015) Structure-activity studies of Wnt/β-catenin inhibition in the niclosamide chemotype: Identification of derivatives with improved drug exposure. Bioorg Med Chem 23:5829–5838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Costabile G, d’Angelo I, Rampioni G, Bondì R, Pompili B, Ascenzioni F, Mitidieri E, di Villa D, Bianca R, Sorrentino R, Miro A, Quaglia F, Imperi F, Leoni L, Ungaro F (2015) Toward repositioning niclosamide for antivirulence therapy of Pseudomonas aeruginosa lung infections: Development of inhalable formulations through nanosuspension technology. Mol Pharm 12:2604–2617

    Article  CAS  PubMed  Google Scholar 

  71. Fichman V, Mota-Damasceno CG, Procópio-Azevedo AC, Almeida-Silva F, de Macedo PM, Medeiros DM, Astacio GSM, Zancopé-Oliveira RM, Almeida-Paes R, Freitas DFS, Gutierrez-Galhardo MC (2022) Pulmonary sporotrichosis caused by Sporothrix brasiliensis: A 22-year, single-center, retrospective cohort study. J Fungi 8:536

    Article  CAS  Google Scholar 

  72. Barini E, Miccoli A, Tinarelli F, Mulholland K, Kadri H, Khanim F, Stojanovski L, Read KD, Burness K, Blow JJ, Mehellou Y, Muqit MMK (2018) The anthelmintic drug niclosamide and its analogues activate the parkinson’s disease associated protein kinase PINK1. ChemBioChem 19:425–429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lima MA, Freitas DFS, Oliveira RVC, Fichman V, Varon AG, Freitas AD, Lamas CC, Andrade HB, Veloso VG, Almeida-Paes R, Almeida-Silva F, Zancopé-Oliveira RM, de Macedo PM, Valle ACF, Silva MTT, Araújo AQC, Gutierrez-Galhardo MC (2022) Meningeal sporotrichosis due to Sporothrix brasiliensis: A 21-year cohort study from a brazilian reference center. J Fungi 9:17

    Article  Google Scholar 

  74. Madrid H, Cano J, Gené J, Bonifaz A, Toriello C, Guarro J (2009) Sporothrix globosa, a pathogenic fungus with widespread geographical distribution. Rev Iberoam Micol 26:218–222

    Article  PubMed  Google Scholar 

  75. Oliveira HC, Joffe LS, Simon KS, Castelli RF, Reis FCG, Bryan AM, Borges BS, Medeiros LCS, Bocca AL, Del Poeta M, Rodrigues ML (2020) Fenbendazole controls in vitro growth, virulence potential, and animal infection in the Cryptococcus model. Antimicrob Agents Chemother 64:e00286-e320

    Article  PubMed  PubMed Central  Google Scholar 

  76. Garcia-Rubio R, Gonzalez-Jimenez I, Lucio J, Mellado E (2021) Characterization of Aspergillus fumigatus cross-resistance between clinical and DMI azole drugs. Appl Environ Microbiol 87:e02539-e2620

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was partially funded by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (grant number E-26/201.441/2021), Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant numbers 405653/2021-2 and 403627/2023-0), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (grant numbers 21/2551-0001974-3 and 23/2551-0000503-4), Programa Inova Fiocruz (grant number PRES-008-FIO-22-2-11) and Programa Jovens Pesquisadores (INI/Fiocruz, grant number INI-003-FIO-19-2-7). R.M.Z-O is supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant number 308315/2021-9) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (grant number E-26/200.381/2023).

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Authors and Affiliations

  1. Laboratório de Biofísica de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Mariana Lucy Mesquita Ramos & Susana Frases

  2. Laboratório de Micologia, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil

    Fernando Almeida-Silva, Vanessa Brito de Souza Rabello, Juliana Nahal, Maria Helena Galdino Figueiredo-Carvalho, Andrea Reis Bernardes-Engemann, Rosely Maria Zancopé-Oliveira & Rodrigo Almeida-Paes

  3. Laboratório de Micologia, Faculdade de Medicina, Universidade Federal Do Rio Grande, Rio Grande, RS, Brazil

    Vanice Rodrigues Poester & Melissa Orzechowski Xavier

  4. Westerdijk Fungal Biodiversity Institute of the KNAW, Utrecht, The Netherlands

    Wieland Meyer

  5. Rede Micologia – FAPERJ, Rio de Janeiro, RJ, Brazil

    Susana Frases & Rodrigo Almeida-Paes

Authors
  1. Mariana Lucy Mesquita Ramos
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  2. Fernando Almeida-Silva
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  3. Vanessa Brito de Souza Rabello
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  4. Juliana Nahal
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  5. Maria Helena Galdino Figueiredo-Carvalho
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  6. Andrea Reis Bernardes-Engemann
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  7. Vanice Rodrigues Poester
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  8. Melissa Orzechowski Xavier
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  9. Wieland Meyer
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  10. Rosely Maria Zancopé-Oliveira
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  11. Susana Frases
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  12. Rodrigo Almeida-Paes
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Correspondence to Susana Frases or Rodrigo Almeida-Paes.

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Susana Frases and Rodrigo Almeida-Paes are authors share senior position.

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Ramos, M.L.M., Almeida-Silva, F., de Souza Rabello, V.B. et al. In vitro activity of the anthelmintic drug niclosamide against Sporothrix spp. strains with distinct genetic and antifungal susceptibility backgrounds. Braz J Microbiol (2024). https://doi.org/10.1007/s42770-024-01301-5

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