Whole-Genome and Targeted-Amplicon Sequencing of Fluconazole-Susceptible and -Resistant Candida parapsilosis Isolates from Kuwait Reveals a Previously Undescribed N1132D Polymorphism in <i>CDR1</i>
Mohammad Asadzadeh, Mohammed Dashti, Suhail Ahmad, Wadha Alfouzan, Abbas Alameer
Abstract
Candida parapsilosis is an opportunistic yeast pathogen causing invasive candidiasis in susceptible patients, surpassing even Candida albicans in frequency in some centers/geographical areas, and causing ∼35% of all candidemia cases in neonates (1–5). Fluconazole resistance among clinical C. parapsilosis isolates is an emerging problem and typically involves Y132F mutation in ERG11, occurring in 31% to 100% of azole-resistant isolates (5, 6). Additional mechanisms include overexpression of efflux pumps CDR1 and MDR1, possibly due to activating mutations in their transcriptional regulators, TAC1 and MRR1, respectively. However, missense mutations in transcriptional regulators TAC1 and MRR1 do not always correlate with overexpression of CDR1 and MDR1 (7, 8). This study performed next-generation sequencing (NGS) to identify novel mutations in target genes involved in conferring resistance to fluconazole in clinical C. parapsilosis isolates in Kuwait.