Synergism Between the Antidepressant Sertraline and Caspofungin As an Approach to Minimise the Virulence and Resistance in the Dermatophyte

Overview

Journal J Fungi (Basel)

Date 2022 Aug 26

PMID 36012803

Authors

Carlos H Lopes Rocha

Flaviane M Galvao Rocha

Tamires A Bitencourt

Maira P Martins

Pablo R Sanches

Antonio Rossi

Nilce M Martinez-Rossi

Affiliations

Soon will be listed here.

Abstract

is responsible for several superficial human mycoses. Novel strategies aimed at controlling this pathogen are being investigated. The objective of this study was to evaluate the antifungal activity of the antidepressant sertraline (SRT), either alone or in combination with caspofungin (CASP). We calculated the minimum inhibitory concentrations of SRT and CASP against . Interactions between SRT and CASP were evaluated using a broth microdilution chequerboard. We assessed the differential expression of cultivated in the presence of SRT or combinations of SRT and CASP. We used MTT and violet crystal assays to compare the effect of SRT alone on biofilms with that of the synergistic combination of SRT and CASP. A human nail infection assay was performed. SRT alone, or in combination with CASP, exhibited antifungal activity against SRT targets genes involved in the biosyntheses of cell wall and ergosterol. Furthermore, the metabolic activity of the biofilm and its biomass were affected by SRT and the combination of SRT and CASP. SRT alone, or in combination, shows potential as an approach to minimise resistance and reduce virulence.

Citing Articles

The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the Dermatophyte : A Comprehensive Analysis.

Rocha C, Galvao Rocha F, Sanches P, Rossi A, Martinez-Rossi N Genes (Basel). 2025; 16(2).

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The Antidepressant Sertraline Affects Cell Signaling and Metabolism in .

Galvao-Rocha F, Rocha C, Martins M, Sanches P, Bitencourt T, Sachs M J Fungi (Basel). 2023; 9(2).

PMID: 36836389 PMC: 9961077. DOI: 10.3390/jof9020275.

Dermatophytic Biofilms: Characteristics, Significance and Treatment Approaches.

Markantonatou A, Samaras K, Vyzantiadis T J Fungi (Basel). 2023; 9(2).

PMID: 36836342 PMC: 9960790. DOI: 10.3390/jof9020228.

Alternative Splicing in Occurs in Efflux Pump Transcripts in Response to Antifungal Drugs.

Lopes M, Bitencourt T, Sanches P, Martins M, Oliveira V, Rossi A J Fungi (Basel). 2022; 8(8).

PMID: 36012866 PMC: 9410333. DOI: 10.3390/jof8080878.

References

Lang E, Bitencourt T, Peres N, Lopes L, Silva L, Cazzaniga R . The stuA gene controls development, adaptation, stress tolerance, and virulence of the dermatophyte Trichophyton rubrum. Microbiol Res. 2020; 241:126592. DOI: 10.1016/j.micres.2020.126592. View

Fazolin Petrucelli M, Matsuda J, Peroni K, Sanches P, Silva Jr W, Beleboni R . The Transcriptional Profile of Co-Cultured with Human Keratinocytes Shows New Insights about Gene Modulation by Terbinafine. Pathogens. 2019; 8(4). PMC: 6963840. DOI: 10.3390/pathogens8040274. View

Badali H, Mohammadi R, Mashedi O, de Hoog G, Meis J . In vitro susceptibility patterns of clinically important Trichophyton and Epidermophyton species against nine antifungal drugs. Mycoses. 2015; 58(5):303-7. DOI: 10.1111/myc.12315. View

Cong L, Liao Y, Yang S, Yang R . In Vitro Antifungal Activity of Sertraline and Synergistic Effects in Combination with Antifungal Drugs against Planktonic Forms and Biofilms of Clinical Trichosporon asahii Isolates. PLoS One. 2016; 11(12):e0167903. PMC: 5145214. DOI: 10.1371/journal.pone.0167903. View

Gomez-Lopez A, Cuenca-Estrella M, Mellado E, Rodriguez-Tudela J . In vitro evaluation of combination of terbinafine with itraconazole or amphotericin B against Zygomycota. Diagn Microbiol Infect Dis. 2003; 45(3):199-202. DOI: 10.1016/s0732-8893(02)00509-6. View

Baghi N, Shokohi T, Badali H, Makimura K, Rezaei-Matehkolaei A, Abdollahi M . In vitro activity of new azoles luliconazole and lanoconazole compared with ten other antifungal drugs against clinical dermatophyte isolates. Med Mycol. 2016; 54(7):757-63. DOI: 10.1093/mmy/myw016. View

Trevino-Rangel R, Villanueva-Lozano H, Mendez-Galomo K, Solis-Villegas E, Becerril-Garcia M, Montoya A . In vivo evaluation of the antifungal activity of sertraline against Aspergillus fumigatus. J Antimicrob Chemother. 2018; 74(3):663-666. DOI: 10.1093/jac/dky455. View

Martinez-Rossi N, Bitencourt T, Peres N, Lang E, Gomes E, Quaresemin N . Dermatophyte Resistance to Antifungal Drugs: Mechanisms and Prospectus. Front Microbiol. 2018; 9:1108. PMC: 5986900. DOI: 10.3389/fmicb.2018.01108. View

Brilhante R, Aguiar L, Sales J, Dos Santos Araujo G, Pereira V, de Aquino Pereira-Neto W . biofilm-forming ability of dermatophytes using dog and cat hair: an ethically viable approach for an infection model. Biofouling. 2019; 35(4):392-400. DOI: 10.1080/08927014.2019.1599361. View

10.

Cowen L, Sanglard D, Howard S, Rogers P, Perlin D . Mechanisms of Antifungal Drug Resistance. Cold Spring Harb Perspect Med. 2014; 5(7):a019752. PMC: 4484955. DOI: 10.1101/cshperspect.a019752. View

11.

Heller I, Leitner S, Dierich M, Lass-Florl C . Serotonin (5-HT) enhances the activity of amphotericin B against Aspergillus fumigatus in vitro. Int J Antimicrob Agents. 2004; 24(4):401-4. DOI: 10.1016/j.ijantimicag.2004.03.021. View

12.

de Hoog S, Monod M, Dawson T, Boekhout T, Mayser P, Graser Y . Skin Fungi from Colonization to Infection. Microbiol Spectr. 2017; 5(4). PMC: 11687524. DOI: 10.1128/microbiolspec.FUNK-0049-2016. View

13.

Martins M, Silva L, Rossi A, Sanches P, Souza L, Martinez-Rossi N . Global Analysis of Cell Wall Genes Revealed Putative Virulence Factors in the Dermatophyte . Front Microbiol. 2019; 10:2168. PMC: 6761320. DOI: 10.3389/fmicb.2019.02168. View

14.

Fortwendel J, Juvvadi P, Pinchai N, Perfect B, Alspaugh J, Perfect J . Differential effects of inhibiting chitin and 1,3-{beta}-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus. Antimicrob Agents Chemother. 2008; 53(2):476-82. PMC: 2630655. DOI: 10.1128/AAC.01154-08. View

15.

Liu S, Hou Y, Chen X, Gao Y, Li H, Sun S . Combination of fluconazole with non-antifungal agents: a promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery. Int J Antimicrob Agents. 2014; 43(5):395-402. DOI: 10.1016/j.ijantimicag.2013.12.009. View

16.

Caballero U, Eraso E, Quindos G, Jauregizar N . In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against . Pharmaceutics. 2021; 13(9). PMC: 8468219. DOI: 10.3390/pharmaceutics13091333. View

17.

Monod M, Feuermann M, Salamin K, Fratti M, Makino M, Alshahni M . Trichophyton rubrum Azole Resistance Mediated by a New ABC Transporter, TruMDR3. Antimicrob Agents Chemother. 2019; 63(11). PMC: 6811443. DOI: 10.1128/AAC.00863-19. View

18.

Ashburn T, Thor K . Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004; 3(8):673-83. DOI: 10.1038/nrd1468. View

19.

Yamada T, Yaguchi T, Salamin K, Guenova E, Feuermann M, Monod M . MFS1, a Pleiotropic Transporter in Dermatophytes That Plays a Key Role in Their Intrinsic Resistance to Chloramphenicol and Fluconazole. J Fungi (Basel). 2021; 7(7). PMC: 8303221. DOI: 10.3390/jof7070542. View

20.

Devane C, Liston H, Markowitz J . Clinical pharmacokinetics of sertraline. Clin Pharmacokinet. 2002; 41(15):1247-66. DOI: 10.2165/00003088-200241150-00002. View