Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii
Summary Cryptococcosis is an invasive mycosis caused mainly by Cryptococcus gattii and C. neoformans and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such a...
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| creator | Rehem, Amanda Rodrigues da Gama Viveiro, Letícia Rampazzo De Souza Santos, Evelyn Luzia do Carmo, Paulo Henrique Fonseca da Silva, Newton Soares Junqueira, Juliana Campos Scorzoni, Liliana |
| description | Summary
Cryptococcosis is an invasive mycosis caused mainly by
Cryptococcus gattii
and
C. neoformans
and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against
Cryptococcus
spp
.
However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against
C. neoformans
and
C. gattii.
In this study, DH inhibited the growth of several
C. neoformans
and
C. gattii
strains at concentrations ranging from 15.62 to 62.50 µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 µg/mL. In biofilm, DH treatment reduced
Cryptococcus
spp. biomass at a level comparable to AMB, with a significant reduction (85%) for
C. neoformans
biofilms. The metabolic activity of
C. neoformans
and
C. gattii
biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of
C. neoformans
and
C. gattii,
opening perspectives for further studies with DH
in vivo
. |
| doi_str_mv | 10.1007/s12223-024-01164-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3045118390</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3045118390</sourcerecordid><originalsourceid>FETCH-LOGICAL-c326t-685fd0626846e2b11761a55b6312e6a96dbde364fd1b095aa7fc0206f2c39ddb3</originalsourceid><addsrcrecordid>eNp9kU2LFDEQhoMo7rj6BzxIgxcvral8VHcfl2H9gAUveg7pfMxm6U7GJA3OvzfurIoePBR1qKfeKngIeQn0LVA6vCvAGOM9ZaKnACh6eER2MA6in7jEx2RHKcheImcX5Fkpd5QiFZw9JRd8RMkExx3ZrmINfosHvXQ62lY1zCH5sKyd896Z2iXf2W1J310N0XW3J5uTuV1SDtZ1-qBDLLXb59OxJpOM2UoXXfIprzqW-8i_ZgddawjPyROvl-JePPRL8vX99Zf9x_7m84dP-6ub3nCGtcdRekuR4SjQsRlgQNBSzsiBOdQT2tk6jsJbmOkktR68oYyiZ4ZP1s78krw55x5z-ra5UtUainHLotuPW1GcCgkw8ok29PU_6F3acmzfKd4OwzCJkTeKnSmTUynZeXXMYdX5pICqn1LUWYpqUtS9FAVt6dVD9Davzv5e-WWhAfwMlDaKB5f_3P5P7A-40pkr</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3117179483</pqid></control><display><type>article</type><title>Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii</title><source>SpringerNature Journals</source><creator>Rehem, Amanda Rodrigues ; da Gama Viveiro, Letícia Rampazzo ; De Souza Santos, Evelyn Luzia ; do Carmo, Paulo Henrique Fonseca ; da Silva, Newton Soares ; Junqueira, Juliana Campos ; Scorzoni, Liliana</creator><creatorcontrib>Rehem, Amanda Rodrigues ; da Gama Viveiro, Letícia Rampazzo ; De Souza Santos, Evelyn Luzia ; do Carmo, Paulo Henrique Fonseca ; da Silva, Newton Soares ; Junqueira, Juliana Campos ; Scorzoni, Liliana</creatorcontrib><description>Summary
Cryptococcosis is an invasive mycosis caused mainly by
Cryptococcus gattii
and
C. neoformans
and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against
Cryptococcus
spp
.
However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against
C. neoformans
and
C. gattii.
In this study, DH inhibited the growth of several
C. neoformans
and
C. gattii
strains at concentrations ranging from 15.62 to 62.50 µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 µg/mL. In biofilm, DH treatment reduced
Cryptococcus
spp. biomass at a level comparable to AMB, with a significant reduction (85%) for
C. neoformans
biofilms. The metabolic activity of
C. neoformans
and
C. gattii
biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of
C. neoformans
and
C. gattii,
opening perspectives for further studies with DH
in vivo
.</description><identifier>ISSN: 0015-5632</identifier><identifier>ISSN: 1874-9356</identifier><identifier>EISSN: 1874-9356</identifier><identifier>DOI: 10.1007/s12223-024-01164-1</identifier><identifier>PMID: 38652436</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Amphotericin B ; Antifungal activity ; Applied Microbiology ; Biocompatibility ; Biofilms ; Biomedical and Life Sciences ; Cryptococcosis ; Cryptococcus ; Cryptococcus gattii ; Cryptococcus neoformans ; Drug resistance ; Duloxetine ; Electron micrographs ; Environmental Engineering/Biotechnology ; Fluconazole ; Fungi ; Fungicidal activity ; Fungicides ; Immunology ; In vivo methods and tests ; Life Sciences ; Microbiology ; Mycosis ; Norepinephrine ; Original Article ; Planktonic cells ; Serotonin ; Serotonin uptake inhibitors</subject><ispartof>Folia microbiologica, 2024-12, Vol.69 (6), p.1247-1254</ispartof><rights>Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-685fd0626846e2b11761a55b6312e6a96dbde364fd1b095aa7fc0206f2c39ddb3</cites><orcidid>0000-0002-0178-6653 ; 0000-0001-5029-5810 ; 0000-0003-1746-9289 ; 0000-0001-6452-9278 ; 0000-0001-6646-6856 ; 0000-0002-4738-7041 ; 0000-0003-3186-885X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12223-024-01164-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12223-024-01164-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38652436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rehem, Amanda Rodrigues</creatorcontrib><creatorcontrib>da Gama Viveiro, Letícia Rampazzo</creatorcontrib><creatorcontrib>De Souza Santos, Evelyn Luzia</creatorcontrib><creatorcontrib>do Carmo, Paulo Henrique Fonseca</creatorcontrib><creatorcontrib>da Silva, Newton Soares</creatorcontrib><creatorcontrib>Junqueira, Juliana Campos</creatorcontrib><creatorcontrib>Scorzoni, Liliana</creatorcontrib><title>Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii</title><title>Folia microbiologica</title><addtitle>Folia Microbiol</addtitle><addtitle>Folia Microbiol (Praha)</addtitle><description>Summary
Cryptococcosis is an invasive mycosis caused mainly by
Cryptococcus gattii
and
C. neoformans
and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against
Cryptococcus
spp
.
However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against
C. neoformans
and
C. gattii.
In this study, DH inhibited the growth of several
C. neoformans
and
C. gattii
strains at concentrations ranging from 15.62 to 62.50 µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 µg/mL. In biofilm, DH treatment reduced
Cryptococcus
spp. biomass at a level comparable to AMB, with a significant reduction (85%) for
C. neoformans
biofilms. The metabolic activity of
C. neoformans
and
C. gattii
biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of
C. neoformans
and
C. gattii,
opening perspectives for further studies with DH
in vivo
.</description><subject>Amphotericin B</subject><subject>Antifungal activity</subject><subject>Applied Microbiology</subject><subject>Biocompatibility</subject><subject>Biofilms</subject><subject>Biomedical and Life Sciences</subject><subject>Cryptococcosis</subject><subject>Cryptococcus</subject><subject>Cryptococcus gattii</subject><subject>Cryptococcus neoformans</subject><subject>Drug resistance</subject><subject>Duloxetine</subject><subject>Electron micrographs</subject><subject>Environmental Engineering/Biotechnology</subject><subject>Fluconazole</subject><subject>Fungi</subject><subject>Fungicidal activity</subject><subject>Fungicides</subject><subject>Immunology</subject><subject>In vivo methods and tests</subject><subject>Life Sciences</subject><subject>Microbiology</subject><subject>Mycosis</subject><subject>Norepinephrine</subject><subject>Original Article</subject><subject>Planktonic cells</subject><subject>Serotonin</subject><subject>Serotonin uptake inhibitors</subject><issn>0015-5632</issn><issn>1874-9356</issn><issn>1874-9356</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kU2LFDEQhoMo7rj6BzxIgxcvral8VHcfl2H9gAUveg7pfMxm6U7GJA3OvzfurIoePBR1qKfeKngIeQn0LVA6vCvAGOM9ZaKnACh6eER2MA6in7jEx2RHKcheImcX5Fkpd5QiFZw9JRd8RMkExx3ZrmINfosHvXQ62lY1zCH5sKyd896Z2iXf2W1J310N0XW3J5uTuV1SDtZ1-qBDLLXb59OxJpOM2UoXXfIprzqW-8i_ZgddawjPyROvl-JePPRL8vX99Zf9x_7m84dP-6ub3nCGtcdRekuR4SjQsRlgQNBSzsiBOdQT2tk6jsJbmOkktR68oYyiZ4ZP1s78krw55x5z-ra5UtUainHLotuPW1GcCgkw8ok29PU_6F3acmzfKd4OwzCJkTeKnSmTUynZeXXMYdX5pICqn1LUWYpqUtS9FAVt6dVD9Davzv5e-WWhAfwMlDaKB5f_3P5P7A-40pkr</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Rehem, Amanda Rodrigues</creator><creator>da Gama Viveiro, Letícia Rampazzo</creator><creator>De Souza Santos, Evelyn Luzia</creator><creator>do Carmo, Paulo Henrique Fonseca</creator><creator>da Silva, Newton Soares</creator><creator>Junqueira, Juliana Campos</creator><creator>Scorzoni, Liliana</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0178-6653</orcidid><orcidid>https://orcid.org/0000-0001-5029-5810</orcidid><orcidid>https://orcid.org/0000-0003-1746-9289</orcidid><orcidid>https://orcid.org/0000-0001-6452-9278</orcidid><orcidid>https://orcid.org/0000-0001-6646-6856</orcidid><orcidid>https://orcid.org/0000-0002-4738-7041</orcidid><orcidid>https://orcid.org/0000-0003-3186-885X</orcidid></search><sort><creationdate>20241201</creationdate><title>Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii</title><author>Rehem, Amanda Rodrigues ; da Gama Viveiro, Letícia Rampazzo ; De Souza Santos, Evelyn Luzia ; do Carmo, Paulo Henrique Fonseca ; da Silva, Newton Soares ; Junqueira, Juliana Campos ; Scorzoni, Liliana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-685fd0626846e2b11761a55b6312e6a96dbde364fd1b095aa7fc0206f2c39ddb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amphotericin B</topic><topic>Antifungal activity</topic><topic>Applied Microbiology</topic><topic>Biocompatibility</topic><topic>Biofilms</topic><topic>Biomedical and Life Sciences</topic><topic>Cryptococcosis</topic><topic>Cryptococcus</topic><topic>Cryptococcus gattii</topic><topic>Cryptococcus neoformans</topic><topic>Drug resistance</topic><topic>Duloxetine</topic><topic>Electron micrographs</topic><topic>Environmental Engineering/Biotechnology</topic><topic>Fluconazole</topic><topic>Fungi</topic><topic>Fungicidal activity</topic><topic>Fungicides</topic><topic>Immunology</topic><topic>In vivo methods and tests</topic><topic>Life Sciences</topic><topic>Microbiology</topic><topic>Mycosis</topic><topic>Norepinephrine</topic><topic>Original Article</topic><topic>Planktonic cells</topic><topic>Serotonin</topic><topic>Serotonin uptake inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rehem, Amanda Rodrigues</creatorcontrib><creatorcontrib>da Gama Viveiro, Letícia Rampazzo</creatorcontrib><creatorcontrib>De Souza Santos, Evelyn Luzia</creatorcontrib><creatorcontrib>do Carmo, Paulo Henrique Fonseca</creatorcontrib><creatorcontrib>da Silva, Newton Soares</creatorcontrib><creatorcontrib>Junqueira, Juliana Campos</creatorcontrib><creatorcontrib>Scorzoni, Liliana</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Folia microbiologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rehem, Amanda Rodrigues</au><au>da Gama Viveiro, Letícia Rampazzo</au><au>De Souza Santos, Evelyn Luzia</au><au>do Carmo, Paulo Henrique Fonseca</au><au>da Silva, Newton Soares</au><au>Junqueira, Juliana Campos</au><au>Scorzoni, Liliana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii</atitle><jtitle>Folia microbiologica</jtitle><stitle>Folia Microbiol</stitle><addtitle>Folia Microbiol (Praha)</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>69</volume><issue>6</issue><spage>1247</spage><epage>1254</epage><pages>1247-1254</pages><issn>0015-5632</issn><issn>1874-9356</issn><eissn>1874-9356</eissn><abstract>Summary
Cryptococcosis is an invasive mycosis caused mainly by
Cryptococcus gattii
and
C. neoformans
and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against
Cryptococcus
spp
.
However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against
C. neoformans
and
C. gattii.
In this study, DH inhibited the growth of several
C. neoformans
and
C. gattii
strains at concentrations ranging from 15.62 to 62.50 µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 µg/mL. In biofilm, DH treatment reduced
Cryptococcus
spp. biomass at a level comparable to AMB, with a significant reduction (85%) for
C. neoformans
biofilms. The metabolic activity of
C. neoformans
and
C. gattii
biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of
C. neoformans
and
C. gattii,
opening perspectives for further studies with DH
in vivo
.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>38652436</pmid><doi>10.1007/s12223-024-01164-1</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-0178-6653</orcidid><orcidid>https://orcid.org/0000-0001-5029-5810</orcidid><orcidid>https://orcid.org/0000-0003-1746-9289</orcidid><orcidid>https://orcid.org/0000-0001-6452-9278</orcidid><orcidid>https://orcid.org/0000-0001-6646-6856</orcidid><orcidid>https://orcid.org/0000-0002-4738-7041</orcidid><orcidid>https://orcid.org/0000-0003-3186-885X</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | Folia microbiologica, 2024-12, Vol.69 (6), p.1247-1254 |
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| source | SpringerNature Journals |
| subjects | Amphotericin B Antifungal activity Applied Microbiology Biocompatibility Biofilms Biomedical and Life Sciences Cryptococcosis Cryptococcus Cryptococcus gattii Cryptococcus neoformans Drug resistance Duloxetine Electron micrographs Environmental Engineering/Biotechnology Fluconazole Fungi Fungicidal activity Fungicides Immunology In vivo methods and tests Life Sciences Microbiology Mycosis Norepinephrine Original Article Planktonic cells Serotonin Serotonin uptake inhibitors |
| title | Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii |
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