Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species
Abstract Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Crypto...
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Veröffentlicht in: | Medical mycology (Oxford) 2020-10, Vol.58 (7), p.906-912 |
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creator | Brilhante, Raimunda Sâmia Nogueira Gotay, Wilker Jose Perez Pereira, Vandbergue Santos de Oliveira, Jonathas Sales Pereira-Neto, Waldemiro Aquino Castelo-Branco, Débora de Souza Collares Maia Cordeiro, Rossana de Aguiar Sidrim, José Júlio Costa Rocha, Marcos Fábio Gadelha |
description | Abstract
Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs. |
doi_str_mv | 10.1093/mmy/myz140 |
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Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs.</description><identifier>ISSN: 1369-3786</identifier><identifier>EISSN: 1460-2709</identifier><identifier>DOI: 10.1093/mmy/myz140</identifier><identifier>PMID: 32016364</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><ispartof>Medical mycology (Oxford), 2020-10, Vol.58 (7), p.906-912</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c317t-38c4bc7ae844aefed8b328188fbaf62c1fa8a9445e06c28ec26352c50c82c18b3</citedby><cites>FETCH-LOGICAL-c317t-38c4bc7ae844aefed8b328188fbaf62c1fa8a9445e06c28ec26352c50c82c18b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32016364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brilhante, Raimunda Sâmia Nogueira</creatorcontrib><creatorcontrib>Gotay, Wilker Jose Perez</creatorcontrib><creatorcontrib>Pereira, Vandbergue Santos</creatorcontrib><creatorcontrib>de Oliveira, Jonathas Sales</creatorcontrib><creatorcontrib>Pereira-Neto, Waldemiro Aquino</creatorcontrib><creatorcontrib>Castelo-Branco, Débora de Souza Collares Maia</creatorcontrib><creatorcontrib>Cordeiro, Rossana de Aguiar</creatorcontrib><creatorcontrib>Sidrim, José Júlio Costa</creatorcontrib><creatorcontrib>Rocha, Marcos Fábio Gadelha</creatorcontrib><title>Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species</title><title>Medical mycology (Oxford)</title><addtitle>Med Mycol</addtitle><description>Abstract
Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs.</description><issn>1369-3786</issn><issn>1460-2709</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kU1rGzEQhkVoSNwkl_yAoEuhFDbWx1qrPRrTLwjkkpwX7Viyla6kzUobuv4r_bORY7fQS04zvPPwMjMvQteU3FJS87lz09xNO1qSEzSjpSAFq0j9Ifdc1AWvpDhHH2N8IoRWNeNn6JwzQgUX5Qz9Wfpkzeg3qsMKkn2xacLB4H4ITqet2lmvsfJrDNsuDHv1KG2U9THhvlP-VwreAgbddfGNbW0wtnNxb7Qapj4FCABjxF4HEwanfJz_p29UStZiCK7v9G8cew1Wx0t0alQX9dWxXqDHb18fVj-Ku_vvP1fLuwI4rVLBJZQtVErLslTa6LVsOZNUStMqIxhQo6Sqy3KhiQAmNTDBFwwWBGQeZvgCfT745vOeRx1T42zcX6PyvmNsGF-QmlBCREa_HFAYQoyDNk0_WKeGqaGk2YfR5DCaQxgZvjn6jq3T63_o3-9n4NMBCGP_ntErlYCY0w</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Brilhante, Raimunda Sâmia Nogueira</creator><creator>Gotay, Wilker Jose Perez</creator><creator>Pereira, Vandbergue Santos</creator><creator>de Oliveira, Jonathas Sales</creator><creator>Pereira-Neto, Waldemiro Aquino</creator><creator>Castelo-Branco, Débora de Souza Collares Maia</creator><creator>Cordeiro, Rossana de Aguiar</creator><creator>Sidrim, José Júlio Costa</creator><creator>Rocha, Marcos Fábio Gadelha</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20201001</creationdate><title>Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species</title><author>Brilhante, Raimunda Sâmia Nogueira ; Gotay, Wilker Jose Perez ; Pereira, Vandbergue Santos ; de Oliveira, Jonathas Sales ; Pereira-Neto, Waldemiro Aquino ; Castelo-Branco, Débora de Souza Collares Maia ; Cordeiro, Rossana de Aguiar ; Sidrim, José Júlio Costa ; Rocha, Marcos Fábio Gadelha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317t-38c4bc7ae844aefed8b328188fbaf62c1fa8a9445e06c28ec26352c50c82c18b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brilhante, Raimunda Sâmia Nogueira</creatorcontrib><creatorcontrib>Gotay, Wilker Jose Perez</creatorcontrib><creatorcontrib>Pereira, Vandbergue Santos</creatorcontrib><creatorcontrib>de Oliveira, Jonathas Sales</creatorcontrib><creatorcontrib>Pereira-Neto, Waldemiro Aquino</creatorcontrib><creatorcontrib>Castelo-Branco, Débora de Souza Collares Maia</creatorcontrib><creatorcontrib>Cordeiro, Rossana de Aguiar</creatorcontrib><creatorcontrib>Sidrim, José Júlio Costa</creatorcontrib><creatorcontrib>Rocha, Marcos Fábio Gadelha</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Medical mycology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brilhante, Raimunda Sâmia Nogueira</au><au>Gotay, Wilker Jose Perez</au><au>Pereira, Vandbergue Santos</au><au>de Oliveira, Jonathas Sales</au><au>Pereira-Neto, Waldemiro Aquino</au><au>Castelo-Branco, Débora de Souza Collares Maia</au><au>Cordeiro, Rossana de Aguiar</au><au>Sidrim, José Júlio Costa</au><au>Rocha, Marcos Fábio Gadelha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species</atitle><jtitle>Medical mycology (Oxford)</jtitle><addtitle>Med Mycol</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>58</volume><issue>7</issue><spage>906</spage><epage>912</epage><pages>906-912</pages><issn>1369-3786</issn><eissn>1460-2709</eissn><abstract>Abstract
Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32016364</pmid><doi>10.1093/mmy/myz140</doi><tpages>7</tpages></addata></record> |
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title | Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species |
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