Difference in virulence between fluconazole-susceptible and fluconazole-resistant Candida albicans in a mouse model

Summary Two Candida albicans isolates were collected from a HIV‐positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU‐S), minimal inhibitory concentration (MIC) = 0.25 mg l−1] and the second aft...

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Veröffentlicht in:Mycoses 2011-09, Vol.54 (5), p.e522-e530
Hauptverfasser: Schulz, Bettina, Weber, Kai, Schmidt, Axel, Borg-von Zepelin, Margarete, Ruhnke, Markus
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container_issue 5
container_start_page e522
container_title Mycoses
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creator Schulz, Bettina
Weber, Kai
Schmidt, Axel
Borg-von Zepelin, Margarete
Ruhnke, Markus
description Summary Two Candida albicans isolates were collected from a HIV‐positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU‐S), minimal inhibitory concentration (MIC) = 0.25 mg l−1] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU‐R, MIC = 64 mg l−1). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU‐S isolate survived the experiment when FLU was given. However, when FLU was absent, the mortality of the FLU‐S isolate was higher than that of the FLU‐R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU‐S isolate and a more intense biofilm‐building activity compared with the FLU‐R isolate. The FLU‐R isolate highly up‐regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. The results showed that FLU‐S and FLU‐R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.
doi_str_mv 10.1111/j.1439-0507.2010.01970.x
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One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU‐S), minimal inhibitory concentration (MIC) = 0.25 mg l−1] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU‐R, MIC = 64 mg l−1). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU‐S isolate survived the experiment when FLU was given. However, when FLU was absent, the mortality of the FLU‐S isolate was higher than that of the FLU‐R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU‐S isolate and a more intense biofilm‐building activity compared with the FLU‐R isolate. The FLU‐R isolate highly up‐regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. 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The results showed that FLU‐S and FLU‐R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.</description><subject>adherence</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antifungal Agents - pharmacology</subject><subject>biofilm</subject><subject>Biofilms</subject><subject>Candida</subject><subject>Candida albicans</subject><subject>Candida albicans - classification</subject><subject>Candida albicans - drug effects</subject><subject>Candida albicans - isolation &amp; purification</subject><subject>Candida albicans - pathogenicity</subject><subject>Candidiasis - microbiology</subject><subject>Candidiasis - pathology</subject><subject>Cell Adhesion</subject><subject>Cell Line</subject><subject>Disease Models, Animal</subject><subject>DNA, Fungal - genetics</subject><subject>Drug Resistance, Fungal</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - microbiology</subject><subject>fluconazole</subject><subject>Fluconazole - pharmacology</subject><subject>Gene expression</subject><subject>Genotype</subject><subject>Growth rate</subject><subject>HIV Infections - complications</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Male</subject><subject>MDR1 protein</subject><subject>Mice</subject><subject>Mortality</subject><subject>Mycological Typing Techniques</subject><subject>Proteinase</subject><subject>resistance</subject><subject>Rodent Diseases - microbiology</subject><subject>Rodent Diseases - pathology</subject><subject>Secretion</subject><subject>Survival Analysis</subject><subject>Virulence</subject><subject>virulence factors</subject><issn>0933-7407</issn><issn>1439-0507</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EotvCX0C5ccoyjh1_HDigtBSkAhIC8XGxbGciefEmS5zQLb--TresxAl88MfM-449fggpKKxpHi82a8qZLqEGua4gR4FqCev9A7I6Jh6SFWjGSslBnpDTlDYAVOpKPCYnFRVQUwUrks5D1-GIvcci9MWvMM7x7uBwukbsiy7Ofujt7yFimebkcTcFF7GwfftXbsQU0mT7qWhyKrS2sNEFb_u01LXFdpgT5rnF-IQ86mxM-PR-PSOfX198at6UVx8u3zavrkrPmYLSedEhq1uhlXPaoe6YFZ7y_F7leG6Ya0ApASqrwFdW2LpWPofQVUp0np2R54e6u3H4OWOazDbkBmK0PebXGJ2_UlBR838qldK8rjinWakOSj8OKY3Ymd0Ytna8MRTMwsZszILALAjMwsbcsTH7bH12f8nsttgejX9gZMHLg-A6RLz578Lm3bdm2WV_efBnELg_-u34wwjJZG2-vL80qvlefWRfwZyzWzZrrjo</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Schulz, Bettina</creator><creator>Weber, Kai</creator><creator>Schmidt, Axel</creator><creator>Borg-von Zepelin, Margarete</creator><creator>Ruhnke, Markus</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope><scope>M7N</scope></search><sort><creationdate>201109</creationdate><title>Difference in virulence between fluconazole-susceptible and fluconazole-resistant Candida albicans in a mouse model</title><author>Schulz, Bettina ; Weber, Kai ; Schmidt, Axel ; Borg-von Zepelin, Margarete ; Ruhnke, Markus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4380-bc6fe35d698bb9be9f3a6c14ffe8b4197490e77002a80c2a6a558c0e7eb286fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>adherence</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antifungal Agents - pharmacology</topic><topic>biofilm</topic><topic>Biofilms</topic><topic>Candida</topic><topic>Candida albicans</topic><topic>Candida albicans - classification</topic><topic>Candida albicans - drug effects</topic><topic>Candida albicans - isolation &amp; purification</topic><topic>Candida albicans - pathogenicity</topic><topic>Candidiasis - microbiology</topic><topic>Candidiasis - pathology</topic><topic>Cell Adhesion</topic><topic>Cell Line</topic><topic>Disease Models, Animal</topic><topic>DNA, Fungal - genetics</topic><topic>Drug Resistance, Fungal</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - microbiology</topic><topic>fluconazole</topic><topic>Fluconazole - pharmacology</topic><topic>Gene expression</topic><topic>Genotype</topic><topic>Growth rate</topic><topic>HIV Infections - complications</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Male</topic><topic>MDR1 protein</topic><topic>Mice</topic><topic>Mortality</topic><topic>Mycological Typing Techniques</topic><topic>Proteinase</topic><topic>resistance</topic><topic>Rodent Diseases - microbiology</topic><topic>Rodent Diseases - pathology</topic><topic>Secretion</topic><topic>Survival Analysis</topic><topic>Virulence</topic><topic>virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schulz, Bettina</creatorcontrib><creatorcontrib>Weber, Kai</creatorcontrib><creatorcontrib>Schmidt, Axel</creatorcontrib><creatorcontrib>Borg-von Zepelin, Margarete</creatorcontrib><creatorcontrib>Ruhnke, Markus</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Mycoses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schulz, Bettina</au><au>Weber, Kai</au><au>Schmidt, Axel</au><au>Borg-von Zepelin, Margarete</au><au>Ruhnke, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Difference in virulence between fluconazole-susceptible and fluconazole-resistant Candida albicans in a mouse model</atitle><jtitle>Mycoses</jtitle><addtitle>Mycoses</addtitle><date>2011-09</date><risdate>2011</risdate><volume>54</volume><issue>5</issue><spage>e522</spage><epage>e530</epage><pages>e522-e530</pages><issn>0933-7407</issn><eissn>1439-0507</eissn><abstract>Summary Two Candida albicans isolates were collected from a HIV‐positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU‐S), minimal inhibitory concentration (MIC) = 0.25 mg l−1] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU‐R, MIC = 64 mg l−1). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU‐S isolate survived the experiment when FLU was given. However, when FLU was absent, the mortality of the FLU‐S isolate was higher than that of the FLU‐R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU‐S isolate and a more intense biofilm‐building activity compared with the FLU‐R isolate. The FLU‐R isolate highly up‐regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. The results showed that FLU‐S and FLU‐R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21605180</pmid><doi>10.1111/j.1439-0507.2010.01970.x</doi><tpages>9</tpages></addata></record>
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source MEDLINE; Wiley Journals
subjects adherence
Animal models
Animals
Antifungal Agents - pharmacology
biofilm
Biofilms
Candida
Candida albicans
Candida albicans - classification
Candida albicans - drug effects
Candida albicans - isolation & purification
Candida albicans - pathogenicity
Candidiasis - microbiology
Candidiasis - pathology
Cell Adhesion
Cell Line
Disease Models, Animal
DNA, Fungal - genetics
Drug Resistance, Fungal
Epithelial cells
Epithelial Cells - microbiology
fluconazole
Fluconazole - pharmacology
Gene expression
Genotype
Growth rate
HIV Infections - complications
Human immunodeficiency virus
Humans
Male
MDR1 protein
Mice
Mortality
Mycological Typing Techniques
Proteinase
resistance
Rodent Diseases - microbiology
Rodent Diseases - pathology
Secretion
Survival Analysis
Virulence
virulence factors
title Difference in virulence between fluconazole-susceptible and fluconazole-resistant Candida albicans in a mouse model
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