Abstract
The emergence of drug resistance in microbial pathogens provides a poignant example of an evolutionary process with a profound impact on human health. Fungal drug resistance poses a particular concern given the limited number of clinically useful antifungal drugs and the growing population of immunocompromised individuals vulnerable to life-threatening fungal disease [1]. The efficacy of most antifungal drugs is compromised either by host toxicity, fungistatic rather than fungicidal activity, or by the emergence of drug resistance. Recent studies have revealed that compromising the function of the molecular chaperone Hsp90 can render resistant pathogens more responsive to treatment and can thwart the evolution of fungal drug resistance [2].
Highlights
The emergence of drug resistance in microbial pathogens provides a poignant example of an evolutionary process with a profound impact on human health
By stabilizing key cellular regulators, Hsp90 can buffer the expression of genetic variation such that it accumulates in a silent state and is exposed when Hsp90 function is compromised, such as by stress [3,4]
The azoles are the most widely deployed class of antifungals. They exert fungistatic activity by inhibiting the biosynthesis of ergosterol, the major sterol of fungal cell membranes. They inhibit the activity of lanosterol 14a-demethylase (Erg11) in the ergosterol biosynthetic pathway and result in the accumulation of a toxic sterol intermediate that results in cell membrane stress [2]
Summary
The emergence of drug resistance in microbial pathogens provides a poignant example of an evolutionary process with a profound impact on human health. Hsp90 has yet another distinct role in fungal evolution: by stabilizing unmutated regulators of cellular signaling, Hsp90 enables stress responses required for survival of drug exposure and for the phenotypic consequences of diverse resistance mutations. Hsp90 Enables the Emergence and Maintenance of Resistance to the Azole Antifungals in the Model Yeast Saccharomyces cerevisiae and the Leading Fungal Pathogen of Humans, Candida albicans (Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
