scholarly journals Effect of antimycotic agents on the activity of aspartyl proteinases secreted by Candida albicans

2003 ◽  
Vol 52 (3) ◽  
pp. 247-249 ◽  
Author(s):  
Martin Schaller ◽  
Nikola Krnjaic ◽  
Markus Niewerth ◽  
Gerald Hamm ◽  
Bernhard Hube ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Proteinase Inhibitors ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Immunodeficiency Virus ◽  
Antimycotic Agent ◽  
Pepstatin A ◽  
Aspartyl Proteinases

The inhibitory effect of human immunodeficiency virus (HIV) proteinase inhibitors amprenavir and saquinavir and antifungal agents terbinafine, ketoconazole, amphotericin B and ciclopiroxolamine on aspartyl proteinases (Saps) secreted by Candida albicans was tested in an in vitro spectophotometric assay. As expected, both HIV proteinase inhibitors showed a significant inhibitory effect on Sap activity, which was comparable to that of the classical aspartyl proteinase inhibitor pepstatin A (P < 0.001). Antifungal drugs such as ketoconazole, terbinafine and amphotericin B had no, or only minor, inhibitory effects on proteolytic activity. In contrast, a significant reduction in Sap activity could be demonstrated during treatment with the antifungal agent ciclopiroxolamine (P < 0.001). These results point to a multiple effect of this antimycotic agent and might explain the reduced adherence of C. albicans to human epithelial cells at subinhibitory doses.

scholarly journals Effects of the Human Immunodeficiency Virus (HIV) Proteinase Inhibitors Saquinavir and Indinavir on In Vitro Activities of Secreted Aspartyl Proteinases of Candida albicans Isolates from HIV-Infected Patients

1999 ◽  
Vol 43 (8) ◽  
pp. 2038-2042 ◽  
Author(s):  
Hans C. Korting ◽  
Martin Schaller ◽  
Gabriele Eder ◽  
Gerald Hamm ◽  
Ursula Böhmer ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Candida Albicans ◽  
Proteinase Inhibitors ◽  
Oral Candidiasis ◽  
Proteinase Activity ◽  
Dependent Manner ◽  
Immunodeficiency Virus ◽  
Dose Dependent ◽  
Pepstatin A

ABSTRACT The effects of therapeutically relevant concentrations of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on the in vitro proteinase activity of Candida albicans were investigated with isolates from HIV-infected and uninfected patients with oral candidiasis. After exposure to the HIV proteinase inhibitors, proteinase activity was significantly reduced in a dose-dependent manner. These inhibitory effects, which were similar to that of pepstatin A, and the reduced virulence phenotype in experimental candidiasis after application of saquinavir indicate the usefulness of these HIV proteinase inhibitors as potential anticandidal agents.

Inhibition of granulocyte phagocytosis of Candida albicans by amphotericin B

1978 ◽  
Vol 24 (4) ◽  
pp. 363-364 ◽  
Author(s):  
C. K. Chan ◽  
Edward Balish
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Phagocytic Activity ◽  
Inhibitory Effect ◽  
Marked Inhibitory Effect

Phagocytic activity of PMN's in five healthy and five burned patients were measured in vitro. Addition of 1 μg per millilitre of amphotericin B to the assay produced a marked inhibitory effect of the phagocytic activity of PMN against C. albicans.

scholarly journals Candida albicans Secreted Aspartyl Proteinases in Virulence and Pathogenesis

2003 ◽  
Vol 67 (3) ◽  
pp. 400-428 ◽  
Author(s):  
Julian R. Naglik ◽  
Stephen J. Challacombe ◽  
Bernhard Hube
Keyword(s):  
Candida Albicans ◽  
Proteinase Inhibitors ◽  
Host Immune System ◽  
Human Proteins ◽  
Candida Infections ◽  
Human Infections ◽  
Host Cell Membranes ◽  
Aspartyl Proteinases

SUMMARY Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

scholarly journals Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro.

1997 ◽  
Vol 41 (3) ◽  
pp. 617-623 ◽  
Author(s):  
G P Moran ◽  
D J Sullivan ◽  
M C Henman ◽  
C E McCreary ◽  
B J Harrington ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amphotericin B ◽  
Oral Candidiasis ◽  
Antifungal Drugs ◽  
Candida Dubliniensis ◽  
Fluconazole Resistance ◽  
Immunodeficiency Virus ◽  
Fluconazole Resistant ◽  
Hiv Negative

Candida dubliniensis is a recently described species of Candida associated with oral candidiasis in human immunodeficiency virus (HIV)-infected individuals. Nineteen oral isolates of C. dubliniensis recovered from 10 HIV-positive and 4 HIV-negative individuals and one vaginal isolate from an additional HIV-negative subject were assessed for fluconazole susceptibility by broth microdilution (BMD), hyphal elongation assessment, and Etest. The susceptibilities of these 20 isolates to itraconazole and amphotericin B and of 10 isolates to ketoconazole were also determined by BMD only. Sixteen of the C. dubliniensis isolates were susceptible to fluconazole (MIC range, 0.125 to 1.0 microgram ml-1), and four (recovered from two AIDS patients) were fluconazole resistant (MIC range, 8 to 32 micrograms ml-1). Fluconazole susceptibility data obtained by hyphal elongation assessment correlated well with results obtained by BMD, but the corresponding Etest MIC results were one to four times higher. All of the isolates tested were found to be sensitive to itraconazole, ketoconazole, and amphotericin B. Sequential exposure of two fluconazole-sensitive (MIC, 0.5 microgram ml-1) C. dubliniensis isolates to increasing concentrations of fluconazole in agar medium resulted in the recovery of derivatives which expressed a stable fluconazole-resistant phenotype (BMD-determined MIC range, 16 to 64 micrograms ml-1), even after a minimum of 10 consecutive subcultures on drug-free medium and following prolonged storage at -70 degrees C. The clonal relationship between the parental isolates and their respective fluconazole-resistant derivatives was confirmed by genomic DNA fingerprinting and karyotype analysis. The results of this study demonstrate that C. dubliniensis is inherently susceptible to commonly used antifungal drugs, that fluconazole resistance does occur in clinical isolates, and that stable fluconazole resistance can be readily induced in vitro following exposure to the drug.

scholarly journals In vitro susceptibility testing of Candida species isolated from blood stream infections to five conventional antifungal drugs

2019 ◽  
pp. 124-129
Author(s):  
Mahdis Hosein Khezri ◽  
Farideh Zaini ◽  
Parivash Kordbache ◽  
Mohammad Ghahri ◽  
Pegah Ardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Candida Species ◽  
Bloodstream Infections ◽  
Blood Stream ◽  
Candida Guilliermondii ◽  
Antifungal Drugs ◽  
In Vitro Susceptibility ◽  
Dose Dependent

Candida is an opportunistic fungal pathogen which can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. In this study, the susceptibility of 196 Candida species isolated from bloodstream infections (BSI) to 5 antifungal drugs were conducted from October 2014 through October 2017. The antifungal drugs used in this study were including fluconazole, itraconazole, voriconazole, Amphotericin B and Caspofungin. From 196 studied isolates, Candida albicans comprised 63.3% of the isolates, followed by C.parapsilosis (18.9 %), C. glabrata (8.7%), C. tropicalis (6.1%), C.krusei (2%) and C.gillermundii (1%). In this study, all isolates of Candida albicans and Candida non-albicans species were completely resistant to voriconazole and itraconazole. Of the 196 Candida isolates, 80 isolates with MIC of 32-16 μg/ml had a dose dependent susceptibility to fluconazole and 111 isolates showed resistance (MIC=64 μg / ml) and only 5 isolates were sensitive (MIC=8 μg / ml) to fluconazole. In this study, out of 196 isolates, 37 isolates were sensitive to amphotericin (MIC=1 μg/ml) and 159 isolates were resistant to amphotericin B (MIC>1 μg/ml). Caspofungin was effective on 104 isolates (MIC<2 μg/ml) and 92 isolates were non-susceptible (MIC>2 μg / ml) to this drug. Out of 124 isolates of Candida albicans, 3 were susceptible, 61 susceptible dose dependent and 60 were resistant to fluconazole. Only 24 isolates were susceptible to amphotericin B and 100 isolates showed resistance to this antifungal drug. Eighty-eight isolates were sensitive to caspofungin and 36 isolates were insensitive. With respect to susceptibility to fluconazole, among 37 isolates of Candida parapsilosis, one was identified as susceptible, 13 isolates were susceptible dose dependent and 13 were resistant. Of these isolates, five were susceptible and 32 isolates were resistant to amphotericin B and caspofungin. Of 12 isolates of Candida tropicalis, 11 showed resistance and 1 was susceptible dose dependent to fluconazole. Of these isolates, 11 were resistant to amphotericin B and 1 isolate was sensitive. Ultimately, only 2 isolates showed susceptibility to caspofungin. Out of 17 isolates of Candida glabrata, 13 isolates were resistant, and 4 isolates had a dose-dependent sensitivity to fluconazole. Eight isolates were susceptible and 9 isolates were resistant to caspofungin. Seven isolates were susceptible and 10 isolates were resistant to amphotericin B. All four Candida krusei isolates showed resistance to the five drugs used in the study. Of the two Candida guilliermondii isolates, both were resistant to amphotericin B, but 1 was sensitive to fluconazole and 1 was identified to be dose-dependent susceptible. One isolate was resistant to and the other one was susceptible to caspofungin. Our findings shows the prevalence of resistant candida species to conventional treatments and indicate that candidemia caused by Candida resistant species is incrasing. Keywords: Candidiasis; Antifungal drugs; Candidemia; Iran

scholarly journals Synergistic Activity of the Tyrocidines, Antimicrobial Cyclodecapeptides from Bacillus aneurinolyticus, with Amphotericin B and Caspofungin against Candida albicans Biofilms

2014 ◽  
Vol 58 (7) ◽  
pp. 3697-3707 ◽  
Author(s):  
Anscha Mari Troskie ◽  
Marina Rautenbach ◽  
Nicolas Delattin ◽  
Johan Arnold Vosloo ◽  
Margitta Dathe ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Membrane Integrity ◽  
Antifungal Drugs ◽  
Infection Model ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Content Type ◽  
Micromolar Range

ABSTRACTTyrocidines are cationic cyclodecapeptides fromBacillus aneurinolyticusthat are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonicCandida albicansin the low-micromolar range. These tyrocidines also preventedC. albicansbiofilm formationin vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of matureC. albicansbiofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using aCaenorhabditis elegansinfection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment.

scholarly journals Dectin-2-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Suresh Ambati ◽  
Emma C. Ellis ◽  
Jianfeng Lin ◽  
Xiaorong Lin ◽  
Zachary A. Lewis ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Effective Dose ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Antifungal Drugs ◽  
Extracellular Matrices ◽  
Content Type ◽  
Order Of Magnitude ◽  
Life Threatening

ABSTRACT Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus cause life-threatening candidiasis, cryptococcosis, and aspergillosis, resulting in several hundred thousand deaths annually. The patients at the greatest risk of developing these life-threatening invasive fungal infections have weakened immune systems. The vulnerable population is increasing due to rising numbers of immunocompromised individuals as a result of HIV infection or immunosuppressed individuals receiving anticancer therapies and/or stem cell or organ transplants. While patients are treated with antifungals such as amphotericin B, all antifungals have serious limitations due to lack of sufficient fungicidal effect and/or host toxicity. Even with treatment, 1-year survival rates are low. We explored methods of increasing drug effectiveness by designing fungicide-loaded liposomes specifically targeted to fungal cells. Most pathogenic fungi are encased in cell walls and exopolysaccharide matrices rich in mannans. Dectin-2 is a mammalian innate immune membrane receptor that binds as a dimer to mannans and signals fungal infection. We coated amphotericin-loaded liposomes with monomers of Dectin-2’s mannan-binding domain, sDectin-2. sDectin monomers were free to float in the lipid membrane and form dimers that bind mannan substrates. sDectin-2-coated liposomes bound orders of magnitude more efficiently to the extracellular matrices of several developmental stages of C. albicans, C. neoformans, and A. fumigatus than untargeted control liposomes. Dectin-2-coated amphotericin B-loaded liposomes reduced the growth and viability of all three species more than an order of magnitude more efficiently than untargeted control liposomes and dramatically decreased the effective dose. Future efforts focus on examining pan-antifungal targeted liposomal drugs in animal models of fungal diseases. IMPORTANCE Invasive fungal diseases caused by Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have mortality rates ranging from 10 to 95%. Individual patient costs may exceed $100,000 in the United States. All antifungals in current use have serious limitations due to host toxicity and/or insufficient fungal cell killing that results in recurrent infections. Few new antifungal drugs have been introduced in the last 2 decades. Hence, there is a critical need for improved antifungal therapeutics. By targeting antifungal-loaded liposomes to α-mannans in the extracellular matrices secreted by these fungi, we dramatically reduced the effective dose of drug. Dectin-2-coated liposomes loaded with amphotericin B bound 50- to 150-fold more strongly to C. albicans, C. neoformans, and A. fumigatus than untargeted liposomes and killed these fungi more than an order of magnitude more efficiently. Targeting drug-loaded liposomes specifically to fungal cells has the potential to greatly enhance the efficacy of most antifungal drugs.

scholarly journals In VitroActivities of Nine Antifungal Drugs against 81 Phialophora and Cyphellophora Isolates

2012 ◽  
Vol 56 (11) ◽  
pp. 6044-6047 ◽  
Author(s):  
Peiying Feng ◽  
M. Javad Najafzadeh ◽  
Jiufeng Sun ◽  
Sarah Ahmed ◽  
Liyan Xi ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Drugs ◽  
Content Type

ABSTRACTCyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.

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