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

Ceballos-Garzón, Andrés; Peñuela, Ana; Valderrama-Beltrán, Sandra; Vargas-Casanova, Yerly; Ariza, Beatriz; Parra-Giraldo, Claudia Marcela

doi:10.3389/fcimb.2023.1136217

Cited by 12 publications

(10 citation statements)

References 58 publications

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“…An epidemiologic study conducted between 2008 and 2010 on candidemia in Latin America found that in Colombia, C. parapsilosis (38.5%) and C. albicans (36.7%) predominated, followed by C. tropicalis (17.4%), C. glabrata (4.6%) and C. guilliermondii (1.8%) [1]. However, in the last years, the situation has changed with the emergence of C. auris throughout the country [20,29]. Despite cases of infections by C. auris being described in several cities, most of the cases have been concentrated on the Atlantic coast [16,29].…”

Section: Discussionmentioning

confidence: 99%

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The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

Álvarez-Moreno

Morales-López

Rodríguez

et al. 2023

JoF

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Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15–9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24–1.97) and 36.4% and 42.3% (0.77; 0.27–2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes.

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Section: Discussionmentioning

confidence: 99%

“…Mutations in the drug-target lanosterol 14-α-demethylase ERG11 gene such as Y132F, K143R and F126L frequently lead to azole resistance in C. auris strains. Additionally, mutations in the transcription factor TAC1 can cause an overexpression of CDR1, which also leads to high-level azole resistance in C. auris [20].…”

Section: Introductionmentioning

confidence: 99%

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

Álvarez-Moreno

Morales-López

Rodríguez

et al. 2023

JoF

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“…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.…”

Section: Isolates Harbouring Non-y132f-g458s Erg11p Substitutionsmentioning

confidence: 92%

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

Mesquida,

Alcoceba,

Padilla

et al. 2024

Mycoses

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BackgroundFluconazole‐resistant Candida parapsilosis is a matter of concern.ObjectivesTo describe fluconazole‐resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole‐resistance profile associated with ERG11p substitutions.Patients/MethodsWe selected fluconazole‐resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility.ResultsOf the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city‐specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild‐type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild‐type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole‐resistance patterns found were: voriconazole‐resistant (74.1%) or voriconazole‐intermediate (25.2%), posaconazole‐resistant (10%) and isavuconazole non‐wild‐type (47.5%). Fluconazole‐resistant and voriconazole non‐wild‐type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non‐wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L.ConclusionsWe detected a recent clonal spread of fluconazole‐resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city‐specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non‐susceptible to voriconazole and rarely posaconazole‐resistant.

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“…The common usage of azoles has contributed to azole-resistance among Candida spp., which complicates the treatment of patients suffering from candidiasis [9,10]. Therefore, searching for natural compounds that are active against fungal pathogens or that improve the activity of commonly used azoles remains a key research aim of modern medicine.…”

Section: Introductionmentioning

confidence: 99%

“…Since azoles influence the structure and functioning of the fungal PM, we considered how a combination of PSZ and SU or CA would impact the growth of C. albicans mutants with alterations in ergosterol (C. albicans KS058 strain, lacking ergosterol in the PM due to the full deletion of ERG11, and three C. albicans strains, 10C1B1I1, 27A5A33A and 9B4B34A, with amino-acid substitutions in Erg11p) or mutations impacting the sphingolipids (SLs) biosynthesis pathway (C. albicans strains lacking FEN1, FEN12 or both genes). We also investigated whether perturbations The common usage of azoles has contributed to azole-resistance among Candida spp., which complicates the treatment of patients suffering from candidiasis [9,10]. Therefore, searching for natural compounds that are active against fungal pathogens or that improve the activity of commonly used azoles remains a key research aim of modern medicine.…”

Section: Introductionmentioning

confidence: 99%

Surfactin and Capric Acid Affect the Posaconazole Susceptibility of Candida albicans Strains with Altered Sterols and Sphingolipids Biosynthesis

Derkacz,

Grzybowska,

Cebula

et al. 2023

IJMS

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Infections caused by Candida spp. pose a continuing challenge for modern medicine, due to widespread resistance to commonly used antifungal agents (e.g., azoles). Thus, there is considerable interest in discovering new, natural compounds that can be used in combination therapy with conventional antibiotics. Here, we investigate whether the natural compounds surfactin and capric acid, in combination with posaconazole, enhance the growth inhibition of C. albicans strains with alterations in sterols and the sphingolipids biosynthesis pathway. We demonstrate that combinations of posaconazole with surfactin or capric acid correspond with the decreased growth of C. albicans strains. Moreover, surfactin and capric acid can independently contribute to the reduced adhesion of C. albicans strains with altered ergosterol biosynthesis to abiotic surfaces (up to 90% reduction in adhesion). A microscopic study of the C. albicans plasma membrane revealed that combinations of those compounds do not correspond with the increased permeabilization of the plasma membrane when compared to cells treated with posaconazole alone. This suggests that the fungistatic effect of posaconazole in combination with surfactin or capric acid is related to the reduction in adhesion of C. albicans.

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

Cited by 12 publications

References 58 publications

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?

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

Surfactin and Capric Acid Affect the Posaconazole Susceptibility of Candida albicans Strains with Altered Sterols and Sphingolipids Biosynthesis

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