Unmasking the Amphotericin B Resistance Mechanisms in Candida haemulonii Species Complex

2020 ◽  
Vol 6 (5) ◽  
pp. 1273-1282 ◽  
Author(s):  
Laura N. Silva ◽  
Simone S. C. Oliveira ◽  
Lucas B. Magalhães ◽  
Valter V. Andrade Neto ◽  
Eduardo C. Torres-Santos ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Species Complex ◽  
Resistance Mechanisms ◽  
Candida Haemulonii

scholarly journals Increasing Prevalence of Multidrug-Resistant Candida haemulonii Species Complex among All Yeast Cultures Collected by a Reference Laboratory over the Past 11 Years

2020 ◽  
Vol 6 (3) ◽  
pp. 110 ◽  
Author(s):  
Soraia Lopes Lima ◽  
Elaine Cristina Francisco ◽  
João Nóbrega de Almeida Júnior ◽  
Daniel Wagner de Castro Lima Santos ◽  
Fabiane Carlesse ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Species Complex ◽  
Antifungal Susceptibility ◽  
Its Region ◽  
Multidrug Resistant ◽  
Sensu Stricto ◽  
Culture Collection ◽  
Reference Laboratory ◽  
Yeast Cultures ◽  
Candida Haemulonii

There is worldwide concern with the increasing rates of infections due to multiresistant Candida isolates reported in tertiary medical centers. We checked for historical trends in terms of prevalence rates and antifungal susceptibility of the Candida haemulonii species complex in our yeast stock culture collected during the last 11 years. The isolates were identified by sequencing the rDNA internal transcribed spacer (ITS) region, and antifungal susceptibility tests for amphotericin B, voriconazole, fluconazole, anidulafungin, and 5-fluorocytosine were performed by the Clinical and Laboratory Standards Institute (CLSI) microbroth method. A total of 49 isolates were identified as Candida haemulonii sensu stricto (n = 21), followed by C. haemulonii var. vulnera (n = 15) and C. duobushaemulonii (n = 13), including 38 isolates cultured from patients with deep-seated Candida infections. The prevalence of the C. haemulonii species complex increased from 0.9% (18 isolates among 1931) in the first period (December 2008 to June 2013) to 1.7% (31 isolates among 1868) in the second period (July 2014 to December 2019) of analysis (p = 0.047). All isolates tested exhibited high minimum inhibition concentrations for amphotericin B and fluconazole, but they remained susceptible to 5-fluorocytosine and anidulafungin. We were able to demonstrate the increased isolation of the multiresistant Candida haemulonii species complex in our culture collection, where most isolates were cultured from patients with deep-seated infections.

scholarly journals Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Amphotericin B and Flucytosine

2012 ◽  
Vol 56 (6) ◽  
pp. 3107-3113 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Species Complex ◽  
Acquired Resistance ◽  
International Study ◽  
Resistance Mechanisms ◽  
Cryptococcus Gattii ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values

ABSTRACTClinical breakpoints (CBPs) are not available for theCryptococcus neoformans-Cryptococcus gattiispecies complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) forC. neoformansandC. gattiiversus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs forC. neoformans(including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs forC. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs forC. neoformanswere evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 μg/ml forC. neoformansVNI (97.2%) andC. gattiiVGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml forC. neoformans(98.5%) andC. gattiinontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 μg/ml forC. gattiinontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml forC. neoformansnontyped (98.6%) andC. gattiiVGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.

Aspergillus terreus Species Complex

2021 ◽  
Author(s):  
Cornelia Lass-Flörl ◽  
Anna-Maria Dietl ◽  
Dimitrios P. Kontoyiannis ◽  
Matthias Brock
Keyword(s):  
At Risk ◽  
Aspergillus Fumigatus ◽  
Human Health ◽  
Amphotericin B ◽  
Species Complex ◽  
Aspergillus Terreus ◽  
Clinical Spectrum ◽  
Chronic Infections ◽  
Epidemiological Surveys ◽  
Risk Patients

Infections due to Aspergillus species are an acute threat to human health; members of the Aspergillus section Fumigati are the most frequently occurring agents, but depending on the local epidemiology, representatives of section Terrei or section Flavi are the second or third most important. Aspergillus terreus species complex is of great interest, as it is usually amphotericin B resistant and displays notable differences in immune interactions in comparison to Aspergillus fumigatus . The latest epidemiological surveys show an increased incidence of A. terreus as well as an expanding clinical spectrum (chronic infections) and new groups of at-risk patients being affected.

scholarly journals Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

2020 ◽  
Vol 69 (6) ◽  
pp. 830-837
Author(s):  
Raimunda Sâmia Nogueira Brilhante ◽  
José Alexandre Telmos Silva ◽  
Géssica dos Santos Araújo ◽  
Vandbergue Santos Pereira ◽  
Wilker Jose Perez Gotay ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
Species Complex ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Species Activity ◽  
Checkerboard Assay

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

scholarly journals Candida duobushaemulonii: An Old But Unreported Pathogen

2020 ◽  
Vol 6 (4) ◽  
pp. 374
Author(s):  
Irene Jurado-Martín ◽  
Cristina Marcos-Arias ◽  
Esther Tamayo ◽  
Andrea Guridi ◽  
Piet W. J. de Groot ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Related Species ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Closely Related Species ◽  
Identification Methods ◽  
Phenotypic Identification ◽  
Candida Intermedia ◽  
Candida Haemulonii

Candidiasis caused by species of the Candida haemulonii complex (Candida haemulonii and Candida duobushaemulonii) and closely related species, Candida auris and Candida pseudohaemulonii are increasing. These species often show reduced susceptibility to antifungal drugs, such as azoles and amphotericin B or, less frequently, echinocandins. However, conventional phenotypic identification methods are unable to accurately differentiate these species and, therefore, their prevalence may have been underestimated. In this study, 150 isolates that were probably misidentified were reanalyzed using two novel PCR approaches. We found that one isolate previously identified in 1996 as Candida intermedia was C. duobushaemulonii, being one of the oldest isolates of this species described to date. We also found that this isolate had reduced susceptibility to fluconazole, itraconazole, and amphotericin B.

scholarly journals Pathogenicity Levels of Colombian Strains of Candida auris and Brazilian Strains of Candida haemulonii Species Complex in Both Murine and Galleria mellonella Experimental Models

2020 ◽  
Vol 6 (3) ◽  
pp. 104
Author(s):  
Julián E. Muñoz ◽  
Laura M. Ramirez ◽  
Lucas dos Santos Dias ◽  
Laura A. Rivas ◽  
Lívia S. Ramos ◽  
...  
Keyword(s):  
Survival Rate ◽  
Species Complex ◽  
Galleria Mellonella ◽  
Experimental Models ◽  
Candida Auris ◽  
Candida Haemulonii ◽  
Virulent Strains ◽  
Inert Surface ◽  
Phagocytosis Index ◽  
Different Levels

Candida auris and Candida haemulonii complex (C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii) are phylogenetically related species that share some physiological features and habits. In the present study, we compared the virulence of these yeast species using two different experimental models: (i) Galleria mellonella larvae to evaluate the survival rate, fungal burden, histopathology and phagocytosis index and (ii) BALB/c mice to evaluate the survival. In addition, the fungal capacity to form biofilm over an inert surface was analyzed. Our results showed that in both experimental models, the animal survival rate was lower when infected with C. auris strains than the C. haemulonii species complex. The hemocytes of G. mellonella showed a significantly reduced ability to phagocytize the most virulent strains forming the C. haemulonii species complex. Interestingly, for C. auris, it was impossible to measure the phagocytosis index due to a general lysis of the hemocytes. Moreover, it was observed a greater capability of biofilm formation by C. auris compared to C. haemulonii species complex. In conclusion, we observed that C. auris and C. haemulonii complex have different levels of pathogenicity in the experimental models employed in the present study.

Amphotericin B: Polyene Resistance Mechanisms

2009 ◽  
pp. 295-305 ◽  
Author(s):  
Elizabeth M. O'Shaughnessy ◽  
Caron A. Lyman ◽  
Thomas J. Walsh
Keyword(s):  
Amphotericin B ◽  
Resistance Mechanisms

scholarly journals Synthetic Lethality Screening Identifies FDA-Approved Drugs that Overcome ATP7B-Mediated Tolerance of Tumor Cells to Cisplatin

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 608 ◽  
Author(s):  
Marta Mariniello ◽  
Raffaella Petruzzelli ◽  
Luca G. Wanderlingh ◽  
Raffaele La Montagna ◽  
Annamaria Carissimo ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Resistance Mechanisms ◽  
Ovarian Cancer Cells ◽  
Tumor Resistance ◽  
Development Of Resistance ◽  
Wide Range ◽  
Important Challenge ◽  
Approved Drugs

Tumor resistance to chemotherapy represents an important challenge in modern oncology. Although platinum (Pt)-based drugs have demonstrated excellent therapeutic potential, their effectiveness in a wide range of tumors is limited by the development of resistance mechanisms. One of these mechanisms includes increased cisplatin sequestration/efflux by the copper-transporting ATPase, ATP7B. However, targeting ATP7B to reduce Pt tolerance in tumors could represent a serious risk because suppression of ATP7B might compromise copper homeostasis, as happens in Wilson disease. To circumvent ATP7B-mediated Pt tolerance we employed a high-throughput screen (HTS) of an FDA/EMA-approved drug library to detect safe therapeutic molecules that promote cisplatin toxicity in the IGROV-CP20 ovarian carcinoma cells, whose resistance significantly relies on ATP7B. Using a synthetic lethality approach, we identified and validated three hits (Tranilast, Telmisartan, and Amphotericin B) that reduced cisplatin resistance. All three drugs induced Pt-mediated DNA damage and inhibited either expression or trafficking of ATP7B in a tumor-specific manner. Global transcriptome analyses showed that Tranilast and Amphotericin B affect expression of genes operating in several pathways that confer tolerance to cisplatin. In the case of Tranilast, these comprised key Pt-transporting proteins, including ATOX1, whose suppression affected ability of ATP7B to traffic in response to cisplatin. In summary, our findings reveal Tranilast, Telmisartan, and Amphotericin B as effective drugs that selectively promote cisplatin toxicity in Pt-resistant ovarian cancer cells and underscore the efficiency of HTS strategy for identification of biosafe compounds, which might be rapidly repurposed to overcome resistance of tumors to Pt-based chemotherapy.

scholarly journals Outbreak of Fungemia among Neonates Caused by Candida haemulonii Resistant to Amphotericin B, Itraconazole, and Fluconazole

2007 ◽  
Vol 45 (6) ◽  
pp. 2025-2027 ◽  
Author(s):  
Z. U. Khan ◽  
N. A. Al-Sweih ◽  
S. Ahmad ◽  
N. Al-Kazemi ◽  
S. Khan ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Haemulonii

Amphotericin B: Polyene Resistance Mechanisms

2017 ◽  
pp. 387-395 ◽  
Author(s):  
Matthew McCarthy ◽  
Elizabeth M. O’Shaughnessy ◽  
Thomas J. Walsh
Keyword(s):  
Amphotericin B ◽  
Resistance Mechanisms
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