Genotypic and phenotypic characterization of Candida albicans Lebanese hospital isolates resistant and sensitive to caspofungin

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dc.contributor.author Toutounji, Maggie
dc.contributor.author Tokajian, Sima
dc.contributor.author Khalaf, Roy A.
dc.date.accessioned 2019-12-03T12:48:18Z
dc.date.available 2019-12-03T12:48:18Z
dc.date.copyright 2019 en_US
dc.date.issued 2019-12-03
dc.identifier.issn 1096-0937 en_US
dc.identifier.uri http://hdl.handle.net/10725/11601
dc.description.abstract The fungus Candida albicans is both a commensal and an opportunistic human pathogen, present as part of the normal human microflora causing 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 hot spots 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, resistance to cell wall disrupting agents, biofilm formation, and cell wall chitin deposition. Five isolates were found to contain mutations with the mutations restricted to resistant strains. Within hot spot 1 substitution at positions S642, T643, L644, R647, and D648 were found, while within hot spot 2 substitutions at positions L1364, T1363, and R1360, W1358 and R1361 were identified with some of the mutations not previously documented. Strains that were 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. 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.title Genotypic and phenotypic characterization of Candida albicans Lebanese hospital isolates resistant and sensitive to caspofungin en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 200300427 en_US
dc.author.idnumber 199736770 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Fungal Genetics and Biology en_US
dc.journal.volume 127 en_US
dc.article.pages 12-22 en_US
dc.keywords Candida albicans en_US
dc.keywords Caspofungin en_US
dc.keywords FKS1 gene en_US
dc.keywords Pathogenicity en_US
dc.keywords Virulence en_US
dc.keywords Resistance en_US
dc.identifier.doi https://doi.org/10.1016/j.fgb.2019.02.008 en_US
dc.identifier.ctation Toutounji, M., Tokajian, S., & Khalaf, R. A. (2019). Genotypic and phenotypic characterization of Candida albicans Lebanese hospital isolates resistant and sensitive to caspofungin. Fungal Genetics and Biology, 127, 12-22. en_US
dc.author.email roy.khalaf@lau.edu.lb en_US
dc.author.email stokjian@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.sciencedirect.com/science/article/pii/S1087184518302056 en_US
dc.orcid.id https://orcid.org/0000-0002-3653-8940 en_US
dc.author.affiliation Lebanese American University en_US

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