+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Antifungal activity of azole compounds CPA18 and CPA109 against azole-susceptible and -resistant strains of Candida albicans

Antifungal activity of azole compounds CPA18 and CPA109 against azole-susceptible and -resistant strains of Candida albicans

Journal of Antimicrobial ChemoTherapy 68(5): 1111-1119

In this study we investigated the in vitro fungistatic and fungicidal activities of CPA18 and CPA109, two azole compounds with original structural features, alone and in combination with fluconazole against fluconazole-susceptible and -resistant Candida albicans strains. Antifungal activities were measured by MIC evaluation and time-kill studies. Azole binding analysis was performed by UV-Vis spectroscopy. Hyphal growth inhibition and filipin and propidium iodide staining assays were used for morphological analysis. An analysis of membrane lipids was also performed to gauge alterations in membrane composition and integrity. Synergism was calculated using fractional inhibitory concentration indices (FICIs). Evaluation of cytotoxicity towards murine macrophages was performed to verify selective antifungal activity. Even though their binding affinity to C. albicans Erg11p is comparable to that of fluconazole, CPA compounds are active against resistant strains of C. albicans with a mutation in ERG11 sequences and/or overexpressing the ABC transporter genes CDR1 and CDR2, which encode ATP-dependent efflux pumps. Moreover, CPA18 is fungistatic, even against the two resistant strains, and was found to be synergistic with fluconazole. Differently from fluconazole and other related azoles, CPA compounds induced marked changes in membrane permeability and dramatic alterations in membrane lipid composition. Our outcomes suggest that CPA compounds are able to overcome major mechanisms of resistance in C. albicans. Also, they are promising candidates for combination treatment that could reduce the toxicity caused by high fluconazole doses, particularly in immunocompromised patients.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 036720575

Download citation: RISBibTeXText

PMID: 23292344

DOI: 10.1093/jac/dks506

Related references

Antifungal activity of essential oils against azole-resistant and azole-susceptible vaginal Candida glabrata strains. Canadian Journal of Microbiology 64(10): 647-663, 2018

The combination effects of MDR inhibitors and azole antifungal agents against azole resistant Candida albicans strains. Clinical Infectious Diseases 25(2): 487, 1997

Restriction fragment length polymorphism analysis of azole-resistant and azole-susceptible Candida albicans strains. Journal of Clinical Microbiology 29(7): 1364-1367, 1991

Nucleotide substitutions in the Candida albicans ERG11 gene of azole-susceptible and azole-resistant clinical isolates. Acta Biochimica Polonica 60(4): 547-552, 2014

Effect of FK463 on adherence of paired azole-susceptible and azole-resistant Candida albicans isolates to epithelial cells. Mycoses 44(Suppl. 1): 81-82, 2001

Inhibition of hyphal growth of azole-resistant strains of Candida albicans by triazole antifungal agents in the presence of lactoferrin-related compounds. Antimicrobial Agents and ChemoTherapy 42(7): 1587-1591, 1998

The lipid composition of azole-sensitive and azole-resistant strains of Candida albicans. Journal of General Microbiology 132(9): 2421-2431, 1986

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains. Journal of Antimicrobial ChemoTherapy 42(6): 747-753, 1999

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains. Journal of Antimicrobial Chemotherapy 42(6): 747-753, 1998

Potent Antifungal Activity of Pure Compounds from Traditional Chinese Medicine Extracts against Six Oral Candida Species and the Synergy with Fluconazole against Azole-Resistant Candida albicans. Evidence-Based Complementary and Alternative Medicine 2012: 106583, 2012

Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrobial Agents and ChemoTherapy 42(2): 241-253, 1998

Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagnostic Microbiology and Infectious Disease 66(4): 373-384, 2010

Comparison of MICs of some Iranian herbal essences against azole resistance and azole susceptible of Candida albicans. Journal Of Medicinal Plants: 27, 37-44, 132, 2008

In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species. Antimicrobial Agents and ChemoTherapy 41(7): 1612-1614, 1997

An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis. Antimicrobial Agents and ChemoTherapy 61(6), 2017