Occidiofungin's chemical stability and in vitro potency against Candida species.

Department of Biological Sciences, Mississippi State University, Mississippi State, Mississippi, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.57). 11/2011; 56(2):765-9. DOI: 10.1128/AAC.05231-11
Source: PubMed

ABSTRACT Occidiofungin is a cyclic glyco-lipopeptide produced by Burkholderia contaminans. MICs against Candida species were between 0.5 and 2.0 μg/ml. Occidiofungin retains its in vitro potency in the presence of 5% and 50% human serum with a minimal lethal concentration (MLC) of 2 and 4 μg/ml, respectively. Time-kill and postantifungal effect (PAFE) experiments of occidiofungin against Candida albicans were performed. The results demonstrate that occidiofungin is fungicidal. Occidiofungin was also found to be a very stable molecule. It is resistant to extreme temperatures and pH and maintains its activity following exposure to gastric proteases.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Burkholderia contaminans strain MS14 produces the antifungal compound occidiofungin, which is responsible for significant antifungal activities against a broad range of plant and animal fungal pathogens. Occidiofungin is a cyclic glycolipopeptide made up of eight amino acids and one xylose. A 56-kb ocf gene cluster was determined to be essential for occidiofungin production. In this study the ocfC gene, which is located downstream of ocfD and upstream of ocfB gene in the ocf gene cluster, was examined. Antifungal activity of the ocfC gene mutant MS14KC1 was reduced against the indicator fungus Geotrichum candidum compared with the wild-type strain. Furthermore, the analysis of the protein sequence suggests that the ocfC gene encodes a glycosyltransferase. Biochemical analyses using NMR and Mass spectroscopy revealed that the ocfC mutant produced the occidiofungin without the xylose. Purified ocfC mutant MS14KC1 product had similar level of bioactivity as compared to the wild-type product. The revertant MS14KC1-R of the ocfC mutant produced the same antifungal activity level on plate assays and the same antifungal compound based on HPLC and mass spectroscopy analysis as the wild type strain MS14. Collectively, the study demonstrates the ocfC gene encodes a glycosyltransferase responsible to add a xylose to the occidiofungin molecule and that the presence of the xylose is not important for antifungal activity against Candida species. The finding provides a novel variant for future studies aimed at evaluating its use for inhibiting clinical and agricultural fungi and the finding could also simplify the chemical synthesis of occidiofungin variants.
    Applied and Environmental Microbiology 02/2013; · 3.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our aim in this study was to evaluate how the chemical stability of silver nanoparticles (SNs) influences their efficacy against Candida albicans and C. glabrata biofilms. Several parameters of SN stability were tested, namely, temperature (50ºC, 70ºC, and 100ºC), pH (5.0 and 9.0), and time of contact (5 h and 24 h) with biofilms. The control was defined as SNs without temperature treatment, pH 7, and 24 h of contact. These colloidal suspensions at 54 mg/L were used to treat mature Candida biofilms (48 h) formed on acrylic. Their efficacy was determined by total biomass and colony-forming unit quantification. Data were analyzed using analysis of variance and the Bonferroni post hoc test (α = 0.05). The temperature and pH variations of SNs did not affect their efficacy against the viable cells of Candida biofilms (P > 0.05). Moreover, the treatment periods were not decisive in terms of the susceptibility of Candida biofilms to SNs. These findings provide an important advantage of SNs that may be useful in the treatment of Candida-associated denture stomatitis.
    Medical mycology. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity produced by the Gram-negative bacterium Burkholderia contaminans. The biosynthetic gene cluster was confirmed to contain two cyclase thioesterases. NMR analysis revealed that the presence of both thioesterases is used to increase the conformational repertoire of the cyclic peptide. The loss of the OcfN cyclic thioesterase by mutagenesis results in a reduction of conformational variants and an appreciable decrease in bioactivity against Candida species. Presumably, the presence of both asparagine and β-hydroxyasparagine variants coordinates the enzymatic function of both of the cyclase thioesterases. OcfN has presumably evolved to be part of the biosynthetic gene cluster due to its ability to produce structural variants that enhance antifungal activity against some fungi. The enhancement of the antifungal activity from the incorporation of an additional cyclase thioesterase into the biosynthetic gene cluster of occidiofungin supports the need to explore new conformational variants of other therapeutic or potentially therapeutic cyclic peptides.
    Journal of Natural Products 02/2013; · 3.29 Impact Factor

Full-text (2 Sources)

Available from
May 20, 2014