Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B
The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinat...
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| Veröffentlicht in: | European journal of clinical microbiology & infectious diseases 2013-04, Vol.32 (4), p.557-564 |
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| creator | de Aguiar Cordeiro, R. Mourão, C. I. Rocha, M. F. G. de Farias Marques, F. J. Teixeira, C. E. C. de Oliveira Miranda, D. F. Neto, L. V. P. Brilhante, R. S. N. de Jesus Pinheiro Gomes Bandeira, T. Sidrim, J. J. C. |
| description | The
Cryptococcus neoformans
species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole–trimethoprim (SMX/TMP) and sulfadiazine–pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of
C. neoformans
and
C. gattii
. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of
C. neoformans
(
n
= 15) and
C. gattii
(
n
= 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of
Cryptococcus
spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in
C. neoformans
and
C. gattii
planktonic cells. Our results highlight the antifungal potential of antifolate drugs. |
| doi_str_mv | 10.1007/s10096-012-1774-8 |
| format | Article |
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Cryptococcus neoformans
species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole–trimethoprim (SMX/TMP) and sulfadiazine–pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of
C. neoformans
and
C. gattii
. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of
C. neoformans
(
n
= 15) and
C. gattii
(
n
= 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of
Cryptococcus
spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in
C. neoformans
and
C. gattii
planktonic cells. Our results highlight the antifungal potential of antifolate drugs.</description><identifier>ISSN: 0934-9723</identifier><identifier>EISSN: 1435-4373</identifier><identifier>DOI: 10.1007/s10096-012-1774-8</identifier><identifier>PMID: 23192488</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Amphotericin B - metabolism ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antifungal agents ; Antifungal Agents - metabolism ; Antiparasitic agents ; Biofilms ; Biofilms - drug effects ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cryptococcosis - microbiology ; Cryptococcus gattii - drug effects ; Cryptococcus gattii - physiology ; Cryptococcus neoformans ; Cryptococcus neoformans - drug effects ; Cryptococcus neoformans - isolation & purification ; Cryptococcus neoformans - physiology ; Drug Combinations ; Drugs ; Environmental Microbiology ; Folic Acid Antagonists - metabolism ; Humans ; Immune system ; Infectious diseases ; Internal Medicine ; Medical equipment ; Medical Microbiology ; Medical sciences ; Microbial Sensitivity Tests ; Pharmacology. Drug treatments ; Pyrimethamine - metabolism ; Sulfadoxine - metabolism ; Trimethoprim, Sulfamethoxazole Drug Combination - metabolism ; Veterinary medicine</subject><ispartof>European journal of clinical microbiology & infectious diseases, 2013-04, Vol.32 (4), p.557-564</ispartof><rights>Springer-Verlag Berlin Heidelberg 2012</rights><rights>2014 INIST-CNRS</rights><rights>Springer-Verlag Berlin Heidelberg 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-2b0bb1b720b42007735ac757fa1599129ea570f3290e91697a9803f3a8b130a23</citedby><cites>FETCH-LOGICAL-c478t-2b0bb1b720b42007735ac757fa1599129ea570f3290e91697a9803f3a8b130a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10096-012-1774-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10096-012-1774-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27369224$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23192488$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Aguiar Cordeiro, R.</creatorcontrib><creatorcontrib>Mourão, C. I.</creatorcontrib><creatorcontrib>Rocha, M. F. G.</creatorcontrib><creatorcontrib>de Farias Marques, F. J.</creatorcontrib><creatorcontrib>Teixeira, C. E. C.</creatorcontrib><creatorcontrib>de Oliveira Miranda, D. F.</creatorcontrib><creatorcontrib>Neto, L. V. P.</creatorcontrib><creatorcontrib>Brilhante, R. S. N.</creatorcontrib><creatorcontrib>de Jesus Pinheiro Gomes Bandeira, T.</creatorcontrib><creatorcontrib>Sidrim, J. J. C.</creatorcontrib><title>Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B</title><title>European journal of clinical microbiology & infectious diseases</title><addtitle>Eur J Clin Microbiol Infect Dis</addtitle><addtitle>Eur J Clin Microbiol Infect Dis</addtitle><description>The
Cryptococcus neoformans
species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole–trimethoprim (SMX/TMP) and sulfadiazine–pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of
C. neoformans
and
C. gattii
. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of
C. neoformans
(
n
= 15) and
C. gattii
(
n
= 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of
Cryptococcus
spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in
C. neoformans
and
C. gattii
planktonic cells. Our results highlight the antifungal potential of antifolate drugs.</description><subject>Amphotericin B - metabolism</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antifungal agents</subject><subject>Antifungal Agents - metabolism</subject><subject>Antiparasitic agents</subject><subject>Biofilms</subject><subject>Biofilms - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cryptococcosis - microbiology</subject><subject>Cryptococcus gattii - drug effects</subject><subject>Cryptococcus gattii - physiology</subject><subject>Cryptococcus neoformans</subject><subject>Cryptococcus neoformans - drug effects</subject><subject>Cryptococcus neoformans - isolation & purification</subject><subject>Cryptococcus neoformans - physiology</subject><subject>Drug Combinations</subject><subject>Drugs</subject><subject>Environmental Microbiology</subject><subject>Folic Acid Antagonists - metabolism</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infectious diseases</subject><subject>Internal Medicine</subject><subject>Medical equipment</subject><subject>Medical Microbiology</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrimethamine - metabolism</subject><subject>Sulfadoxine - metabolism</subject><subject>Trimethoprim, Sulfamethoxazole Drug Combination - metabolism</subject><subject>Veterinary medicine</subject><issn>0934-9723</issn><issn>1435-4373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU2LFDEQhoMo7rj6A7xIQAQvrUmqe9I57g5-wYIXPYckmzgZu5M2lT7MvzfDjB8IXqoO9bxVL_US8pyzN5wx-RZbVduOcdFxKftufEA2vIeh60HCQ7JhCvpOSQFX5AnigTXNKOVjciWAK9GP44YcblKNIU-meqQx7aONle7KcanZZedWpDbmEKcZqUn31Ke9Sc5TXNH5pTZ6ivVIc6DLZNL3mlN01PlpQlozNfOyz9WX6GKit0_Jo2Am9M8u_Zp8ff_uy-5jd_f5w6fdzV3nejnWTlhmLbdSMNuL5ljCYJwcZDB8UIoL5c0gWQChmFd8q6RRI4MAZrQcmBFwTV6f9y4l_1g9Vj1HPHkyyecVNQcBIwfYntCX_6CHvJbU3DWKDzAMSqpG8TPlSkYsPuilxNmUo-ZMn4LQ5yB0C0KfgtBj07y4bF7t7O9_K359vgGvLoBBZ6ZQ2l8j_uEkbJUQfePEmcM2St98-cvif6__BFlSn88</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>de Aguiar Cordeiro, R.</creator><creator>Mourão, C. I.</creator><creator>Rocha, M. F. G.</creator><creator>de Farias Marques, F. J.</creator><creator>Teixeira, C. E. C.</creator><creator>de Oliveira Miranda, D. F.</creator><creator>Neto, L. V. P.</creator><creator>Brilhante, R. S. N.</creator><creator>de Jesus Pinheiro Gomes Bandeira, T.</creator><creator>Sidrim, J. J. C.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope></search><sort><creationdate>20130401</creationdate><title>Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B</title><author>de Aguiar Cordeiro, R. ; Mourão, C. I. ; Rocha, M. F. G. ; de Farias Marques, F. J. ; Teixeira, C. E. C. ; de Oliveira Miranda, D. F. ; Neto, L. V. P. ; Brilhante, R. S. N. ; de Jesus Pinheiro Gomes Bandeira, T. ; Sidrim, J. J. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-2b0bb1b720b42007735ac757fa1599129ea570f3290e91697a9803f3a8b130a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amphotericin B - metabolism</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antifungal agents</topic><topic>Antifungal Agents - metabolism</topic><topic>Antiparasitic agents</topic><topic>Biofilms</topic><topic>Biofilms - drug effects</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cryptococcosis - microbiology</topic><topic>Cryptococcus gattii - drug effects</topic><topic>Cryptococcus gattii - physiology</topic><topic>Cryptococcus neoformans</topic><topic>Cryptococcus neoformans - drug effects</topic><topic>Cryptococcus neoformans - isolation & purification</topic><topic>Cryptococcus neoformans - physiology</topic><topic>Drug Combinations</topic><topic>Drugs</topic><topic>Environmental Microbiology</topic><topic>Folic Acid Antagonists - metabolism</topic><topic>Humans</topic><topic>Immune system</topic><topic>Infectious diseases</topic><topic>Internal Medicine</topic><topic>Medical equipment</topic><topic>Medical Microbiology</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrimethamine - metabolism</topic><topic>Sulfadoxine - metabolism</topic><topic>Trimethoprim, Sulfamethoxazole Drug Combination - metabolism</topic><topic>Veterinary medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Aguiar Cordeiro, R.</creatorcontrib><creatorcontrib>Mourão, C. I.</creatorcontrib><creatorcontrib>Rocha, M. F. G.</creatorcontrib><creatorcontrib>de Farias Marques, F. J.</creatorcontrib><creatorcontrib>Teixeira, C. E. C.</creatorcontrib><creatorcontrib>de Oliveira Miranda, D. F.</creatorcontrib><creatorcontrib>Neto, L. V. P.</creatorcontrib><creatorcontrib>Brilhante, R. S. N.</creatorcontrib><creatorcontrib>de Jesus Pinheiro Gomes Bandeira, T.</creatorcontrib><creatorcontrib>Sidrim, J. J. C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>European journal of clinical microbiology & infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Aguiar Cordeiro, R.</au><au>Mourão, C. I.</au><au>Rocha, M. F. G.</au><au>de Farias Marques, F. J.</au><au>Teixeira, C. E. C.</au><au>de Oliveira Miranda, D. F.</au><au>Neto, L. V. P.</au><au>Brilhante, R. S. N.</au><au>de Jesus Pinheiro Gomes Bandeira, T.</au><au>Sidrim, J. J. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B</atitle><jtitle>European journal of clinical microbiology & infectious diseases</jtitle><stitle>Eur J Clin Microbiol Infect Dis</stitle><addtitle>Eur J Clin Microbiol Infect Dis</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>32</volume><issue>4</issue><spage>557</spage><epage>564</epage><pages>557-564</pages><issn>0934-9723</issn><eissn>1435-4373</eissn><abstract>The
Cryptococcus neoformans
species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole–trimethoprim (SMX/TMP) and sulfadiazine–pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of
C. neoformans
and
C. gattii
. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of
C. neoformans
(
n
= 15) and
C. gattii
(
n
= 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of
Cryptococcus
spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in
C. neoformans
and
C. gattii
planktonic cells. Our results highlight the antifungal potential of antifolate drugs.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>23192488</pmid><doi>10.1007/s10096-012-1774-8</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0934-9723 |
| ispartof | European journal of clinical microbiology & infectious diseases, 2013-04, Vol.32 (4), p.557-564 |
| issn | 0934-9723 1435-4373 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1323813362 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Amphotericin B - metabolism Antibiotics. Antiinfectious agents. Antiparasitic agents Antifungal agents Antifungal Agents - metabolism Antiparasitic agents Biofilms Biofilms - drug effects Biological and medical sciences Biomedical and Life Sciences Biomedicine Cryptococcosis - microbiology Cryptococcus gattii - drug effects Cryptococcus gattii - physiology Cryptococcus neoformans Cryptococcus neoformans - drug effects Cryptococcus neoformans - isolation & purification Cryptococcus neoformans - physiology Drug Combinations Drugs Environmental Microbiology Folic Acid Antagonists - metabolism Humans Immune system Infectious diseases Internal Medicine Medical equipment Medical Microbiology Medical sciences Microbial Sensitivity Tests Pharmacology. Drug treatments Pyrimethamine - metabolism Sulfadoxine - metabolism Trimethoprim, Sulfamethoxazole Drug Combination - metabolism Veterinary medicine |
| title | Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B |
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