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Genotypic and phenotypic characterization of candida albicans Lebanese hospital isolates resistant and sensitive to caspofungin. (c2018)

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dc.contributor.author Toutounji, Maggie Nazih
dc.date.accessioned 2018-10-15T06:21:26Z
dc.date.available 2018-10-15T06:21:26Z
dc.date.copyright 2018 en_US
dc.date.submitted 2018-07-19
dc.identifier.uri http://hdl.handle.net/10725/8627
dc.description.abstract Candida albicans is both a commensal and a significant opportunistic fungal human pathogen, present in the digestive tract and the mouth as a part of the normal human microflora. Overgrowth of C. albicans can cause oral and vaginal candidiasis as well as a number of serious mucosal, and systemic life threatening infections. The antifungal drug caspofungin of the echinocandin family is the latest generation of antifungal drugs to be developed. It functions by inhibiting glucan synthase thus weakening the fungal cell wall leading to death. Recently reports of resistance to caspofungin have been reported mainly through mutations in the FKS encoded subunits of glucan synthase at Hot spot 1 (amino acids 641 to 649, FSTLSLRDP) and hot spot 2 (amino acids 1357 to 1364, DWIRRYTL). Our study aimed at sequencing both hot spots from 16 C. albicans Lebanese hospital isolates resistant and sensitive to caspofungin to determine whether mutations in these hotspots are present, and whether such mutations also impart resistance to our isolates. In addition we wanted to determine any relationship between resistance and pathogenicity related attributes such as virulence, adhesion, filamentation, resistance to cell wall disrupting agents such as Congo red, biofilm formation, and cell wall chitin deposition. Five isolates were found to contain mutations with the mutations restricted to resistant strains. Within hotspot 1 substitution at positions S642, T643, L644, R647, and D648 were found, while within hotspot 2 substitutions at positions L1364, T1363, and R1360, W1358 and R1361 were identified. Interestingly some of the mutations found have not been previously documented. In addition strains that are resistant to caspofungin also showed increased resistance to Congo red but decreased biofilm formation and attenuated virulence in a mouse model of infection. Caspofungin sensitive strains showed decreased resistance to Congo red yet increased virulence and biofilm formation. All filamentous strains were adhesive but only some were virluent. Chitin content analysis showed that caspofungin resistant strains had elevated levels of chitin resulting in cell wall thickening that counters the effect of caspofungin, while sensitive strains showed decreased chitin content. Our results demonstrate an inverse correlation between resistance and virulence whereby resistance is due to thickening of the cell wall preventing the cell from gaining virulence attributes, while a more susceptible cell wall increases susceptibility to drugs but allows increased virulence. en_US
dc.language.iso en en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.subject Candida albicans en_US
dc.subject Drug resistance en_US
dc.subject Fungal cell walls -- Effect of drugs on en_US
dc.subject Hospitals -- Lebanon en_US
dc.title Genotypic and phenotypic characterization of candida albicans Lebanese hospital isolates resistant and sensitive to caspofungin. (c2018) en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201400186 en_US
dc.author.commembers Tokajian, Sima
dc.author.commembers Wex, Brigitte
dc.author.commembers Stephan, Joseph
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc 1 hard copy: xi, 76 leaves; col. ill.; 30 cm. available at RNL. en_US
dc.author.advisor Khalaf, Roy
dc.keywords Candida albicans en_US
dc.keywords Caspofungin en_US
dc.keywords HS1 en_US
dc.keywords HS2 en_US
dc.keywords Chitin en_US
dc.keywords Resistance en_US
dc.keywords Virulence en_US
dc.description.bibliographiccitations Bibliography : leaves 59-76. en_US
dc.identifier.doi https://doi.org/10.26756/th.2018.89 en_US
dc.author.email maggie.toutounji@lau.edu en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US


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