Relationship between in Vitro Resistance, MTL Homozygosity and ERG11 Point Mutations in C. albicans Clinical Isolates in Lebanon. (c2007)

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dc.contributor.author Basma, Raida Habib
dc.date.accessioned 2011-10-21T05:45:06Z
dc.date.available 2011-10-21T05:45:06Z
dc.date.copyright 2007 en_US
dc.date.issued 2011-10-21
dc.date.submitted 2007-02
dc.identifier.uri http://hdl.handle.net/10725/839
dc.description Includes bibliographical references (l. 85-106). en_US
dc.description.abstract The incidence of antifungal resistance is on the increase worldwide and novel drugs are constantly being developed to counter this trend. 125 clinical isolates consisting mainly of Candida albicans (116 samples) were collected from five Lebanese hospitals. The purpose of this study is to first: determine the degree of resistance of Lebanese isolates to four common azoles: Fluconazole (FL), Itraconazole (I'I), Ketoconazole (KE), and Voriconazole (VO), in addition to Amphotericin B (AP) and the newly released echinocandin, Caspofungin (CS) through the E-test method. Second determine any relationship between the allelic compositions of the mating type loci (MTLa, MTL a or MTLa/ a heterozygote) with drug resistance in C. albicans, and third, screen by RFLP for the presence of two common C. albicans ERG 11 point mutations and correlate with drug resistance. Results showed that resistance among C. albicans isolates was highest for IT: 12%, followed by VO: 7.7%, then KE: 6%, FL: 5%, and 0% for CS. Furthermore 11 isolates were heterozygous at the MTL locus (9.5%), 5 of which (45%) were resistant to at least one antifungal drug while only 14 of the 105 heterozygous strains (13%) exhibited similar resistance, indicating a possible relationship between MTL locus homozygosity and resistance. Moreover no relationship between the Dl16E mutation and drug resistance was found, and no homozygous E266D mutants exist In addition, the study revealed the existence of a novel mutation, G407R that occurred frequently and alongside the E266D mutation (70% of isolates assayed were homozygous for G407R and heterozygous for E266D). This mutation was found to be correlated with drug resistance since all the isolates that were resistant to at least one antifungal drug possessed the G407R mutation. Finally this mutation was found to dominate in sputum (41%) and stool isolates (15%). In conclusion resistance to common azoles in Lebanon is low and azole treatment should not be discontinued in favor of newer drugs such as Caspofungin, which should be used as a last resort. en_US
dc.language.iso en en_US
dc.subject Candida albicans en_US
dc.subject Antifungal agents en_US
dc.subject Drug Resistance, Fungal en_US
dc.subject Mycoses en_US
dc.subject Mycoses -- Immunological aspects en_US
dc.title Relationship between in Vitro Resistance, MTL Homozygosity and ERG11 Point Mutations in C. albicans Clinical Isolates in Lebanon. (c2007) en_US
dc.type Thesis en_US
dc.term.submitted Fall en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school Arts and Sciences en_US
dc.author.idnumber 200202660 en_US
dc.author.commembers Dr. Sima Tokajian
dc.author.commembers Dr. Yolande Saab
dc.author.woa OA en_US
dc.description.physdesc 1 bound copy: viii, 106 leaves; 30 cm. available at RNL. en_US
dc.author.division Biology en_US
dc.author.advisor Dr. Roy Khalaf
dc.identifier.doi https://doi.org/10.26756/th.2007.31 en_US
dc.publisher.institution Lebanese American University en_US

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