Pharmaceuticals & Vitamin D : Antifungals


Nylon-3 Polymers to Treat Fungal Infections

UW–Madison researchers have found that nylon-3 polymers developed in their lab display potent antifungal activity against a broad spectrum of common fungal pathogens, with minimal toxicity towards mammalian cells. The polymers have some activity alone, and when used in combination with existing drugs provide synergistic effects against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus strains, including some resistant strains.

Synergistic combination offers efficacy with significantly reduced amounts of drug and corresponding toxicity, which could potentially expand the relevant patient population.

The polymers were designed to resemble host-defense peptides (HDPs), which are natural molecules that exhibit antimicrobial activities.

Treating Fungal Infections with New Forazoline Compounds

UW–Madison researchers have developed antifungal compounds isolated from Actinomadura, a bacterium found in a species of sea squirt. After extensive chemical isolation and characterization, the researchers identified a new class of compounds called ‘Forazolines’ that possess antifungal activity. Forazoline A was shown to be effective against Candida albicans in a mouse model.

Beta-Peptides with Antifungal Activity

UW-Madison researchers have developed a less toxic alternative for treating yeast infections— synthetic beta-peptides with antifungal properties. These relatively short peptides contain cyclically constrained beta-amino acid residues. They are designed to adopt helical conformations that mimic the globally amphiphilic alpha helical conformations of many host-defense peptides, but they remain effective under physiological conditions that render host-defense alpha-peptides inactive against fungal pathogens. Like Amphotericin B, these peptides probably act by disrupting fungal cell walls. In contrast to Amphotericin B, these peptides do not appear to disrupt human red blood cell membranes at concentrations that kill C. albicans.

Recombinant, Attenuated Vaccine for Blastomyces Dermatitidis to Prevent Fungal Infection

UW-Madison researchers have successfully engineered an attenuated, replication-competent strain of B. dermatitidis that is incapable of expressing the cell wall protein WI-1. This recombinant, attenuated strain serves as a highly effective vaccine against the systemic, lethal infectious disease caused by B. dermatitidis and possibly against related fungi. In vitro, the number of lung colony forming units, as a sign of lung infection, revealed a substantial decrease in wild type infection.

The present invention describes use of the genetically engineered fungus as a vaccine given subcutaneously in multiple doses. Dosages can be administered at high levels to provide infection resistance yet low enough so that the fungus is cleared from the body. The researchers are currently conducting in vivo studies with dogs.

Method of Sensitizing Microbial Cells to Antimicrobial Compounds

UW-Madison researchers have developed a method for increasing the uptake of exogenous antimicrobial compounds by bacteria or fungi. The method involves the use of sesquiterpenoid compounds to enhance the permeability of microbial cells, allowing increased uptake of a wide variety of antimicrobial compounds.