Fluconazole‐resistant Candida parapsilosis strains with a Y132F substitution in the ERG11 gene causing invasive infections in a neonatal unit, South Africa. Issue 5 (13th April 2020)

• Record Type: Journal Article
• Authors: Magobo, Rindidzani E.; Lockhart, Shawn R.; Govender, Nelesh P.
• Other Names: Wadula Jeannette investigator.; Rensburg van investigator.; van Rensburg Chris Janse investigator.; Whitelaw Andrew investigator.; Zietsman Inge investigator.; Miller Norman investigator.; Smith Peter investigator.; van Greune Johan investigator.; Brink Adrian investigator.; Hoosen Anwar investigator.; Perovic Olga investigator.; Nchabaleng Maphoshane investigator.; Orth Heidi investigator.; Coovadia Yacoob investigator.; Badenhorst Loekie investigator.; Moolman Johan investigator.; Peer AK investigator.; Govind Chetna investigator.; Kularatne Ranmini investigator.; Bhagoobhai Barry investigator.; Prinsloo Ben investigator.; Haffejee Sumayya investigator.; Simpson John investigator.; Hoyland Greta investigator.; van Schalkwyk Marthinus investigator.; Bowie Glenda investigator.; Hanise Patricia investigator.; Vasaikar Sandeep investigator.; Wende Linda investigator.; Chiller Tom investigator.; Ahlquist‐Cleveland Angela investigator.; Patel Jaymati investigator.;
• Is Part Of: Mycoses. Volume 63:Issue 5(2020)
• Page Start: 471
• Page End: 477
• Publication Date: 2020-04-13
• Subjects: Candida parapsilosis -- candidemia -- ERG11 -- fluconazole resistance -- MRR1 -- South Africa; Pathogenic fungi -- Periodicals; Medical mycology -- Periodicals; 616.969
• DOI: 10.1111/myc.13070
• Languages: English
• ISSNs: 0933-7407

Abstract

Summary: Introduction: The prevalence of azole resistance in C parapsilosis is very low in most parts of the world. However, South Africa has reported an exceptionally high prevalence of azole resistance in C parapsilosis strains isolated from candidaemia cases. We aimed to determine the possible molecular mechanisms of fluconazole resistance in C parapsilosis isolates obtained through surveillance at a large neonatal unit at a South African academic hospital. Methods: We sequenced the ERG11 and MRR1 genes of C parapsilosis isolates recovered from cases of neonatal candidemia, followed by microsatellite genotyping. A total of 73 isolates with antifungal susceptibility results were analysed. Results: Of these, 57 (78%) were resistant, 11 (15%) susceptible dose‐dependent and 5 (7%) susceptible. The most commonly identified amino acid substitution within the ERG11 gene was Y132F in 68% (39/57) of fluconazole‐resistant isolates and none in susceptible isolates. Three amino acid substitutions (R405K, G583R and A619V) and 1 nucleotide deletion at position 1331 were identified within MRR1 gene in 19 (26%) isolates. Microsatellite genotyping grouped isolates into four clusters (50 isolates). Cluster 1 accounted for 23% (17/73) of all cases, cluster 2 for 22% (16/73), cluster 3 for 14% (10/73) and cluster 4 for 10% (7/73). We found an association between cluster type and fluconazole resistance ( P ‐value = .004). Isolates harbouring the Y132F substitution were more likely to belong to a cluster than non‐Y132F isolates. Conclusion: Fluconazole resistance in C parapsilosis strains from a single South African neonatal unit was associated with cluster type and predominantly driven by Y123F amino acid substitutions in the ERG11 gene.