Do Candida albicans Isolates with Borderline Resistant Micafungin MICs Always Harbor FKS1 Hot Spot Mutations?

Abstract

Antifungal susceptibility testing is important in guiding patient therapy due to an increasing number of resistant Candida isolates. In the clinical strain collection of the Austrian resistance report (AURES), a high number of micafungin-resistant C. albicans isolates (18.2% 49/269) was detected in seven different centres in Austria from 2011–2016. Most of these isolates showed a micafungin MIC value that was just above the clinical breakpoint (CB) established by EUCAST (0.016 mg/L). The aim of this study was to analyse whether C. albicans strains showing a micafungin MIC value of 1–2 dilutions above the CB (0.032 mg/L and 0.064 mg/L) are associated with mutations in FKS1 hotspot (HS) regions. 115 C. albicans candidemia strains showing a micafungin MIC one or two dilutions above the EUCAST CB (0.032 mg/L and 0.064 mg/L) were categorized as borderline resistant and screened for mutations in FKS1 HS1, HS2, and HS3 regions, which are known locations for the development of echinocandin resistance. For this purpose, we implemented targeted resequencing utilizing a next generation sequencing technology. No missense mutations could be detected in FKS1 HS1, HS2, and HS3 in any of the 115 isolates, which indicated that resistance conferred by alteration of FKS1 seems unlikely.

Two Candida auris Cases in Germany with No Recent Contact to Foreign Healthcare—Epidemiological and Microbiological Investigations

“…Additionally, the isolate was wildtype at position S639 in the FKS1 gene. A large study from Austria failed to find FKS1 mutations in C. albicans isolates with borderline echinocandin MICs [25]. The fact that our C. auris isolate had no mutation in the FKS1 region is congruent to observations that a mutation is mainly linked to high MICs above 4 mg/L [15].…”

Case Report: Echinocandin-Resistance Candida glabrata FKS Mutants From Patient Following Radical Cystoprostatectomy Due to Muscle-Invasive Bladder Cancer

“…The substitutions were in positions L628, S629, L630, and D632, of which S629 and D632 mutations generated amino acid substitutions, from serine to phenylalanine and from aspartic acid to alanine, respectively ( Table 2 ). The mutations detected in the FKS1 hotspot-1 may be spontaneous and related to clinical echinocandin exposure ( 7 , 23 , 24 ). None of the analysed C. glabrata clinical isolates displayed FKS1 hotspot-2 region mutations.…”

Fungal Whole-Genome Sequencing for Species Identification: From Test Development to Clinical Utilization

“…In addition, the same data generated by WGS also enables anti-microbial resistance (AMR) prediction, a promising area that we are actively exploring for clinical applications of molecular AMR testing (e.g., FKS genotyping for echinocandin resistance in Candida spp. [ 27 , 28 ] and CYP51A genotyping for azole resistance in Aspergillus spp. [ 29 ]).…”