Benincasa Monica, Pacor Sabrina, Wu Wei, Prato Maurizio, Bianco Alberto, Gennaro Renato
Antifungal activity of amphotericin B conjugated to carbon nanotubes Journal Article
In: ACS nano, vol. 5, no. 1, pp. 199–208, 2011, ISSN: 1936-086X.
Abstract | Links | BibTeX | Tags: Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco
@article{benincasa_antifungal_2011,
title = {Antifungal activity of amphotericin B conjugated to carbon nanotubes},
author = {Monica Benincasa and Sabrina Pacor and Wei Wu and Maurizio Prato and Alberto Bianco and Renato Gennaro},
doi = {10.1021/nn1023522},
issn = {1936-086X},
year = {2011},
date = {2011-01-01},
journal = {ACS nano},
volume = {5},
number = {1},
pages = {199--208},
abstract = {Amphotericin B (AMB) has long been considered the most effective drug in the treatment of serious invasive fungal infections. There are, however, major limitations to its use, due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB with sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a collection of reference and clinical fungal strains, in comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f-CNT-AMB 1. Additional studies, aimed at understanding the mechanism of action of the conjugates, suggest a nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.},
keywords = {Amphotericin B, Antifungal Agents, Candida, carbon, Cell Membrane, Deoxycholic Acid, Drug Design, Drug Resistance, Fungal, Humans, I2CT, Jurkat Cells, Kinetics, Membrane Potentials, Nanotubes, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Perreau V. M., Keith G., Holmes W. M., Przykorska A., Santos M. A., Tuite M. F.
The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure Journal Article
In: J Mol Biol, vol. 293, no. 5, pp. 1039-53, 1999, (0022-2836 Journal Article).
Abstract | BibTeX | Tags: *Nucleic, Acid, albicans/*genetics, Anticodon/*chemistry/*genetics/metabolism, Base, Candida, cerevisiae/genetics, Code/genetics, Conformation, Evolution, Fungal/chemistry/genetics/metabolism, Genetic, Gov't, Imidazoles/metabolism, Lead/metabolism, Methylation, Methyltransferases/metabolism, Molecular, Mutation/genetics, Non-P.H.S., Non-U.S., Nucleosides/genetics/metabolism, P.H.S., Ribonucleases/metabolism, RNA, Saccharomyces, Sequence, Ser/*chemistry/*genetics/metabolism, Solutions, Support, Transfer, tRNA, U.S.
@article{,
title = {The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure},
author = { V. M. Perreau and G. Keith and W. M. Holmes and A. Przykorska and M. A. Santos and M. F. Tuite},
year = {1999},
date = {1999-01-01},
journal = {J Mol Biol},
volume = {293},
number = {5},
pages = {1039-53},
abstract = {In many Candida species, the leucine CUG codon is decoded by a tRNA with two unusual properties: it is a ser-tRNA and, uniquely, has guanosine at position 33 (G33). Using a combination of enzymatic (V1 RNase, RnI nuclease) and chemical (Pb(2+), imidazole) probing of the native Candida albicans ser-tRNACAG, we demonstrate that the overall tertiary structure of this tRNA resembles that of a ser-tRNA rather than a leu-tRNA, except within the anticodon arm where there is considerable disruption of the anticodon stem. Using non-modified in vitro transcripts of the C. albicans ser-tRNACAG carrying G, C, U or A at position 33, we demonstrate that it is specifically a G residue at this position that induces the atypical anticodon stem structure. Further quantitative evidence for an unusual structure in the anticodon arm of the G33-tRNA is provided by the observed change in kinetics of methylation of the G at position 37, by purified Escherichia coli m(1)G37 methyltransferase. We conclude that the anticodon arm distortion, induced by a guanosine base at position 33 in the anticodon loop of this novel tRNA, results in reduced decoding ability which has facilitated the evolution of this tRNA without extinction of the species encoding it.},
note = {0022-2836
Journal Article},
keywords = {*Nucleic, Acid, albicans/*genetics, Anticodon/*chemistry/*genetics/metabolism, Base, Candida, cerevisiae/genetics, Code/genetics, Conformation, Evolution, Fungal/chemistry/genetics/metabolism, Genetic, Gov't, Imidazoles/metabolism, Lead/metabolism, Methylation, Methyltransferases/metabolism, Molecular, Mutation/genetics, Non-P.H.S., Non-U.S., Nucleosides/genetics/metabolism, P.H.S., Ribonucleases/metabolism, RNA, Saccharomyces, Sequence, Ser/*chemistry/*genetics/metabolism, Solutions, Support, Transfer, tRNA, U.S.},
pubstate = {published},
tppubtype = {article}
}
Braun A, Hoffmann Jules A, Meister Marie
Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes Journal Article
In: Proc. Natl. Acad. Sci. U.S.A., vol. 95, no. 24, pp. 14337–14342, 1998, ISSN: 0027-8424.
Abstract | BibTeX | Tags: Adipose Tissue, Animals, Candida, Escherichia coli, Fungal, Genotype, Hemocytes, hoffmann, Larva, M3i, Melanins, Micrococcus luteus, Spores
@article{braun_analysis_1998,
title = {Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes},
author = {A Braun and Jules A Hoffmann and Marie Meister},
issn = {0027-8424},
year = {1998},
date = {1998-11-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {95},
number = {24},
pages = {14337--14342},
abstract = {We have analyzed the Drosophila immune response in domino mutant larvae, which are devoid of blood cells. The domino mutants have a good larval viability, but they die as prepupae. We show that, on immune challenge, induction of the genes encoding antimicrobial peptides in the fat body is not affected significantly in the mutant larvae, indicating that hemocytes are not essential in this process. The hemocoele of domino larvae contains numerous live microorganisms, the presence of which induces a weak antimicrobial response in the fat body. A full response is observed only after septic injury. We propose that the fat body cells are activated both by the presence of microorganisms and by injury and that injury potentiates the effect of microorganisms. Survival experiments after an immune challenge showed that domino mutants devoid of blood cells maintain a wild-type resistance to septic injury. This resistance was also observed in mutant larvae in which the synthesis of antibacterial peptides is impaired (immune deficiency larvae) and in mutants that are deficient for humoral melanization (Black cells larvae). However, if domino was combined with either the immune deficiency or the Black cell mutation, the resistance to septic injury was reduced severely. These results establish the relevance of the three immune reactions: phagocytosis, synthesis of antibacterial peptides, and melanization. By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection.},
keywords = {Adipose Tissue, Animals, Candida, Escherichia coli, Fungal, Genotype, Hemocytes, hoffmann, Larva, M3i, Melanins, Micrococcus luteus, Spores},
pubstate = {published},
tppubtype = {article}
}
Santos M. A., Keith G., Tuite M. F.
Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon Journal Article
In: EMBO J, vol. 12, no. 2, pp. 607-16, 1993, (0261-4189 Journal Article).
Abstract | BibTeX | Tags: *Anticodon, *Translation, &, Acid, albicans/*genetics, Base, Candida, Cloning, Conformation, Data, DNA, Fungal, Fungal/chemistry/genetics/isolation, Genes, Genetic, Gov't, Leucine/*genetics, Molecular, Non-U.S., Nucleic, purification, RNA, Sequence, Ser/chemistry/*genetics/isolation, Support, Transfer
@article{,
title = {Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon},
author = { M. A. Santos and G. Keith and M. F. Tuite},
year = {1993},
date = {1993-01-01},
journal = {EMBO J},
volume = {12},
number = {2},
pages = {607-16},
abstract = {From in vitro translation studies we have previously demonstrated the existence of an apparent efficient UAG (amber) suppressor tRNA in the dimorphic fungus Candida albicans (Santos et al., 1990). Using an in vitro assay for termination codon readthrough the tRNA responsible was purified to homogeneity from C.albicans cells. The determined sequence of the purified tRNA predicts a 5'-CAG-3' anticodon that should decode the leucine codon CUG and not the UAG termination codon as originally hypothesized. However, the tRNA(CAG) sequence shows greater nucleotide homology with seryl-tRNAs from the closely related yeast Saccharomyces cerevisiae than with leucyl-tRNAs from the same species. In vitro tRNA-charging studies demonstrated that the purified tRNA(CAG) is charged with Ser. The gene encoding the tRNA was cloned from C.albicans by a PCR-based strategy and DNA sequence analysis confirmed both the structure of the tRNA(CAG) and the absence of any introns in the tRNA gene. The copy number of the tRNA(CAG) gene (1-2 genes per haploid genome) is in agreement with the relatively low abundance (< 0.5% total tRNA) of this tRNA. In vitro translation studies revealed that the purified tRNA(CAG) could induce apparent translational bypass of all three termination codons. However, peptide mapping of in vitro translation products demonstrated that the tRNA(CAG) induces translational misreading in the amino-terminal region of two RNA templates employed, namely the rabbit alpha- and beta-globin mRNAs. These results suggest that the C.albicans tRNA(CAG) is not an 'omnipotent' suppressor tRNA but rather may mediate a novel non-standard translational event in vitro during the translation of the CUG codon. The possible nature of this non-standard translation event is discussed in the context of both the unusual structural features of the tRNA(CAG) and its in vitro behaviour.},
note = {0261-4189
Journal Article},
keywords = {*Anticodon, *Translation, &, Acid, albicans/*genetics, Base, Candida, Cloning, Conformation, Data, DNA, Fungal, Fungal/chemistry/genetics/isolation, Genes, Genetic, Gov't, Leucine/*genetics, Molecular, Non-U.S., Nucleic, purification, RNA, Sequence, Ser/chemistry/*genetics/isolation, Support, Transfer},
pubstate = {published},
tppubtype = {article}
}