Project #11074
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#11074 : Evaluation de la représentativité génétique d'un pool de souches
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Name of Applicant : Emilie Sitterlé
Date of application : 26-02-2018
Unit : Fungal Biology and Pathogenicity
Location : Fernbach-4-33
Phone : 0616894133
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Project context and summary :

Objectives: Our objective was, through whole genome sequencing, to establish a comprehensive repertoire of the non-synonymous polymorphisms (natural polymorphisms and/or mutations of resistance) in genes involved in resistance to azoles and echinocandins. Methods: Two collections of C. albicans clinical isolates were used. The first one consists of 151 epidemiologically-unrelated strains susceptible to antifungal agents. The second one consists of 9 isolates resistant to fluconazole and 1 to fluconazole and caspofungin. The whole genome sequencing was performed on an Illumina HiSeq 2000, generating 100 bp reads (roughly 100X coverage on average). The reads were mapped to the SC5314 reference genome (Assembly 22) using the BWA alignment tool. Then SNPs were detected by GATK and selected with the recommended filters. Using homemade scripts we analyzed the sequences of 5 genes involved in the resistance to azoles (ERG11, TAC1, MRR1 and UPC2) and echinocandins (FKS1) and compared them to the sequences of reference strain SC5314. Results: Among the 151 antifungal susceptible strains we identified 126 distinct natural amino-acid substitutions. Using this repertoire, we identified from the 10 resistant strains, 22 amino-acid substitutions in addition to some of the above-mentioned natural polymorphisms. Among them, 10 have already been associated to azoles or echinocandins resistance. The remaining 12 substitutions are novel putative azoles resistance mutations affecting ERG11 (n=4/11), TAC1 (n=6/7) and UPC2 (n=2/3).

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Project Type : Short
Status : In Progress
Publication : 10.1093/jac/dkz537
Global Satisfaction for this application : Excellent (5/5)

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