Circulation of Fluconazole-ResistantC. albicans, C. aurisandC. parapsilosisBloodstream Isolates Carrying Y132F, K143R or T220L Erg11p Substitutions in Colombia

Abstract

Although Candida spp., is a common cause of bloodstream infections and is often associated with high mortality rates, its resistance to antifungal drugs, and the molecular mechanisms involved have been poorly studied in Colombia. Here, 123 bloodstream isolates of Candida spp. were collected. MALDI-TOF MS identification and fluconazole (FLC) susceptibility patterns were assessed on all isolates. Subsequently, sequencing of ERG11, TAC1 or MRR1, and efflux pumps were performed for resistant isolates. 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%. Erg11 amino acid substitutions associated with FLC-resistance (Y132F, K143R or T220L) were found in 58% of 19 FLC-resistant isolates. Furthermore, novel mutations were found in all genes studied. Regarding efflux pumps, 42% of 19 FLC-resistant Candida spp strains showed significant efflux activity. Finally, six of the 19 FLC-resistant isolates neither harbored resistance-associated mutations nor showed efflux pump activity. Although C. albicans remain the most predominant species, non-C. albicans species comprise a high proportion (62.6%). Among FLC-resistant species, C. auris (70%) and C. parapsilosis (25%) displayed the highest percentages of resistance. In 68% of FLC-resistant isolates, a mechanism that could explain their phenotype was found (e.g. mutations, flux pump activity or both). We provide evidence that endemic isolates harbor amino acid substitutions related with resistance to one of the most used molecules in the hospital setting, with Y132F being the most frequently detected one.

Fluconazole‐resistant Candida parapsilosis complex candidemia and analysis of mutations in the ERG11 gene from Pakistan

“…37 Fluconazole resistance-associated mutations in C. parapsilosis species complex at positions Y132F, K143R, M178T, N283Y and T591C have been reported previously. 10,[38][39][40] The Y132F mutation in the ERG11 gene was responsible for most of our fluconazole resistance strains in this study.…”

Azole resistance: Insights from Y132 substitutions inCandidasterol 14α-demethylase

“…Azole-resistant Candida infections are increasingly becoming a public health concern (Castanheira et al, 2020). Most of the azole-resistant Candida isolates have been linked to substitutions at Y132 in the sterol 14α-demethylase, also known as ERG11 protein (Castanheira et al, 2020; Ceballos-Garzon et al, 2023). As evident from our compilation of data, it seems that Y132F is the only Y132 substitution in C auris, C. parapsilosis , and C. tropicalis (Castanheira et al, 2020; Ceballos-Garzon et al, 2023; Thomaz et al, 2021), whereas Y132H seems to be more frequent than Y132F in C. albicans (Chau et al, 2004).…”

Fluconazole‐resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole‐resistance profiles associated with the Y132F ERG11p substitution

“…6 We confirm that fluconazole resistance in C. parapsilosis is dominated by the presence of the Y132F substitution reported. 7,14,16,[30][31][32][33] Most of our isolates harboured Y132F ± R398I ERG11p substitutions, were included in clonally related genotypes, and were unrelated to genotypes harbouring only the Y132F substitution. Genotypes involving non-Y132F substitution isolates were unrelated and did not seem to associate with vigorous hospital transmission.…”