A Novel Immunocompetent Mouse Model for Testing Antifungal Drugs Against Invasive Candida albicans Infection

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Disseminated Candida infections are life-threatening, necessitating new antifungal drugs due to rising resistance.
• Current in vivo screening methods are resource-intensive, requiring many animals and immunosuppressive agents.
• Immunosuppressants may interfere with drug candidate efficacy, complicating screening results.

Purpose of the Study:

• To develop a novel, efficient in vivo method for screening antifungal drugs against Candida albicans.
• To reduce the number of animals required for antifungal drug screening.
• To eliminate the need for immunosuppressive agents in in vivo antifungal screening.

Main Methods:

• Engineered a red fluorescent protein (RFP)-expressing Candida albicans strain with retained infectivity.
• Utilized immunocompetent mice deficient in murine beta-defensin 1 (mBD-1) to establish non-lethal disseminated infections.
• Employed in vivo imaging to monitor fungal dissemination in real-time and assess drug activity.

Main Results:

• The fluorescent C. albicans strain successfully established non-lethal disseminated infections in mBD-1-deficient mice.
• Real-time in vivo imaging allowed for quantification of fungal dissemination.
• The method enabled visualization of an antifungal peptide mimetic drug's activity in vivo.

Conclusions:

• A novel in vivo imaging approach using fluorescent C. albicans in mBD-1-deficient mice offers an efficient screening platform.
• This method reduces animal usage and avoids confounding effects of immunosuppressive agents.
• The technique facilitates rapid evaluation of new antifungal agents for disseminated Candida infections.