Amy J Karlsson

University of Wisconsin, Madison, Madison, MS, United States

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Publications (6)40.32 Total impact

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    ABSTRACT: Fungal infections are a major challenge to human health that is heightened by pathogen resistance to current therapeutic agents. Previously, we were inspired by host-defense peptides to develop nylon-3 polymers (poly-β-peptides) that are toxic toward the fungal pathogen Candida albicans but exert little effect on mammalian cells. Based on subsequent analysis of structure-activity relationships among antifungal nylon-3 polymers, we have now identified readily prepared cationic homopolymers active against strains of C. albicans that are resistant to the antifungal drugs fluconazole and amphotericin B. These nylon-3 polymers are nonhemolytic. In addition, we have identified cationic-hydrophobic copolymers that are highly active against a second fungal pathogen, Cryptococcus neoformans, and moderately active against a third pathogen, Aspergillus fumigatus.
    Journal of the American Chemical Society 03/2014; · 10.68 Impact Factor
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    ABSTRACT: We report the creation of alkylated poly-N-substituted glycine (peptoid) mimics of antimicrobial lipopeptides with alkyl tails ranging from 5 to 13 carbons. In several cases, alkylation significantly improved the selectivity of the peptoids with no loss in antimicrobial potency. Using this technique, we synthesized an antimicrobial peptoid only 5 monomers in length with selective, broad-spectrum antimicrobial activity as potent as previously reported dodecameric peptoids and the antimicrobial peptide pexiganan.
    Antimicrobial Agents and Chemotherapy 10/2010; 55(1):417-20. · 4.57 Impact Factor
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    ABSTRACT: The fungal pathogen Candida albicans can form biofilms on the surfaces of medical devices that are resistant to drug treatment and provide a reservoir for recurrent infections. The use of fungicidal or fungistatic materials to fabricate or coat the surfaces of medical devices has the potential to reduce or eliminate the incidence of biofilm-associated infections. Here we report on (i) the fabrication of multilayered polyelectrolyte thin films (PEMs) that promote the surface-mediated release of an antifungal β-peptide and (ii) the ability of these films to inhibit the growth of C. albicans on film-coated surfaces. We incorporated a fluorescently labeled antifungal β-peptide into the structures of PEMs fabricated from poly-l-glutamic acid (PGA) and poly-l-lysine (PLL) using a layer-by-layer fabrication procedure. These films remained stable when incubated in culture media at 37 °C and released β-peptide gradually into solution for up to 400 h. Surfaces coated with β-peptide-containing films inhibited the growth of C. albicans , resulting in a 20% reduction of cell viability after 2 h and a 74% decrease in metabolic activity after 7 h when compared to cells incubated on PGA/PLL-coated surfaces without β-peptide. In addition, β-peptide-containing films inhibited hyphal elongation by 55%. These results, when combined, demonstrate that it is possible to fabricate β-peptide-containing thin films that inhibit the growth and proliferation of C. albicans and provide the basis of an approach that could be used to inhibit the formation of C. albicans biofilms on film-coated surfaces. The layer-by-layer approach reported here could ultimately be used to coat the surfaces of catheters, surgical instruments, and other devices to inhibit drug-resistant C. albicans biofilm formation in clinical settings.
    Biomacromolecules 09/2010; 11(9):2321-8. · 5.37 Impact Factor
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    ABSTRACT: Beta-peptides (beta-amino acid oligomers) that mimic the amphiphilic, helical, and cationic properties of natural antimicrobial peptides have previously been shown to display antifungal activity against planktonic Candida albicans cells. Beta-peptides offer several advantages over conventional peptides composed of alpha-amino acid residues, including conformational stability, resistance to proteases, and activity at physiological salt concentrations. We examined sequence-activity relationships toward both planktonic C. albicans cells and C. albicans biofilms, and the results suggest a toxicity mechanism involving membrane disruption. A strategy for fluorescently labeling a beta-peptide without diminishing antifungal activity was devised; labeled beta-peptides penetrated the cell membrane and accumulated in the cytoplasm of both planktonic and biofilm-associated cells. The labeled beta-peptide was detected only in metabolically inactive cells, which suggests that beta-peptide entry is correlated with cell death. The presence of a beta-peptide at a concentration near the minimum inhibitory concentration completely prevented planktonic C. albicans cells from forming a biofilm, suggesting that beta-peptides may be useful in preventing fungal colonization and biofilm formation.
    ACS Chemical Biology 07/2009; 4(7):567-79. · 5.44 Impact Factor
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    ABSTRACT: Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.
    Eukaryotic Cell 07/2007; 6(6):931-9. · 3.59 Impact Factor
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    ABSTRACT: We have discovered that short beta-peptides (9 or 10 residues) designed to adopt globally amphiphilic helical conformations display significant antifungal activity. The most promising beta-peptides cause little lysis of human red blood cells at concentrations that kill Candida albicans, a common human fungal pathogen. Since fungi are eukaryotes, discrimination between fungal and human cells is a significant finding. Our beta-peptides are active under assay conditions that mimic physiological ionic strength; in contrast, alpha-helix-forming host-defense alpha-peptides are inactive against C. albicans under these conditions.
    Journal of the American Chemical Society 11/2006; 128(39):12630-1. · 10.68 Impact Factor