Virulence Factors and Novel Therapies

Current antifungals target a relatively small number of essential fungal-specific gene functions, such as inhibition of ergosterol biosynthesis, cell wall biosynthesis, etc. Developments have been largely limited to improving antifungals through chemical modifications and developing synergistic drug combinations (reviewed in Kontoyiannis & Lewis, 2004).

Will the identification of novel A. fumigatus virulence factors and a more comprehensive understanding of the disease process ultimately lead to the development of novel and more effective therapies? Thus far, drugs targeting fungal virulence factors have not been developed. Neither have genomics-based strategies for discovery of novel antifungal drug targets produced any agents in clinical development (Odds, 2005). However, this does not mean that such novel drugs will not emerge in the future. There are several recent examples for small molecule inhibitors of bacterial virulence factors (Lee et al., 2003): high-throughput screening identified virstatin, a small molecule that inhibits a transcriptional regulator in Vibrio cholerae, prevents the expression of cholera toxin and blocks virulence (Hung et al., 2005). Rational drug design has been used to develop peptide 'pilicides' that inhibit the formation of pili in uropathogenic Escherichia coli (Svensson et al., 2001). However, no 'anti-virulence' compounds have entered clinical use to date.

Perhaps new compounds should be targeted at unique and essential fungal pathways rather than against virulence factors? Elitra Pharmaceuticals (San Diego, CA.) recently performed a genomewide screen to identify essential genes conserved both in S. cerevisiae and C. albicans (Haselbeck et al., 2002). A similar but partial screen was also performed in A. fumigatus, leading to the identification of 20 previously uncharacterized essential genes (Firon et al., 2003). Essential fungal-specific genes can be developed as novel antifungal targets in the future.

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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