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. 2023 Mar 21:13:1136217.
doi: 10.3389/fcimb.2023.1136217. eCollection 2023.

Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia

Andres Ceballos-Garzon  1 , Ana Peñuela  1   2 , Sandra Valderrama-Beltrán  3 , Yerly Vargas-Casanova  1 , Beatriz Ariza  2 , Claudia M Parra-Giraldo  1
Affiliations

Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia

Andres Ceballos-Garzon et al. Front Cell Infect Microbiol. .

Abstract

Methods: Over a four-year period, 123 Candida bloodstream isolates were collected at a quaternary care hospital. The isolates were identified by MALDI-TOF MS and their fluconazole (FLC) susceptibility patterns were assessed according to CLSI guidelines. Subsequently, sequencing of ERG11, TAC1 or MRR1, and efflux pump activity were performed for resistant isolates.

Results: Out of 123 clinical strains,C. albicans accounted for 37.4%, followed by C. tropicalis 26.8%, C. parapsilosis 19.5%, C. auris 8.1%, C. glabrata 4.1%, C. krusei 2.4% and C. lusitaniae 1.6%. Resistance to FLC reached 18%; in addition, a high proportion of isolates were cross-resistant to voriconazole. Erg11 amino acid substitutions associated with FLC-resistance (Y132F, K143R, or T220L) were found in 11/19 (58%) of FLCresistant isolates. Furthermore, novel mutations were found in all genes evaluated. Regarding efflux pumps, 8/19 (42%) of FLC-resistant Candida spp strains showed significant efflux activity. Finally, 6/19 (31%) of FLC-resistant isolates neither harbored resistance-associated mutations nor showed efflux pump activity. Among FLC-resistant species, C. auris 7/10 (70%) and C. parapsilosis 6/24 (25%) displayed the highest percentages of resistance (C. albicans 6/46, 13%).

Discussion: Overall, 68% of FLC-resistant isolates exhibited a mechanism that could explain their phenotype (e.g. mutations, efflux pump activity, or both). We provide evidence that isolates from patients admitted to a Colombian hospital harbor amino acid substitutions related to resistance to one of the most commonly used molecules in the hospital setting, with Y132F being the most frequently detected.

Keywords: Candida species; Colombia; ERG11; Y132F; bloodstream infections; fluconazole resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Species distribution and overall fluconazole susceptibility results. (A) Distribution of the 123 species identified. (B) Percentage of fluconazole resistance. The number of isolates is indicated inside the bars. Susceptible (S) isolates are depicted in blue and resistant (R) isolates in red.
Figure 2
Figure 2
Phylogenetic tree and amino acid substitutions found in fluconazole-resistant isolates of (A) C albicans (CAAL), (B) C auris (CAAU) and (C) C parapsilosis (CAPA). aa., amino acids; FLC, fluconazole; MIC, minimal inhibitory concentration; CA-S., Candida FLC-susceptible. Inside the colored squares, the number of substitutions found is indicated.
Figure 3
Figure 3
Rhodamine 6G (R6G) efflux over time among fluconazole-resistant isolates. Colored lines indicate the concentration of R6G released after the addition of 20 mM glucose (GLU). Data are means ± SD from three experiments. *p < 0.05, **p < 0.01, ***p < 0.001. ****p≤ 0.0001. FLC, fluconazole; MIC, minimal inhibitory concentration.
Figure 4
Figure 4
Schematic representation of the results obtained in this study for the 19 FLC-resistant isolates. In purple C. albicans, light blue C. parapsilosis and yellow C. auris isolates with their respective MICs against FLC. In red font, the mutations found. The green stars indicate isolates with significant efflux pump activity. The size of the circle reflects the number of mutations, those not associated with FLC resistance (blue) and the new mutations (light green).
Figure 5
Figure 5
Countries from which azole-resistant C. parapsilosis carrying ERG11 mutations have been reported, as of February, 2023.
See this image and copyright information in PMC

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