Comparative Pathogenicity of Lomentospora prolificans (Scedosporium prolificans) Isolates from Mexican Patients

Area of Science:

• Medical Mycology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Lomentospora prolificans is an emerging fungal pathogen causing infections in humans.
• Limited treatment options exist for Lomentospora prolificans infections, and antifungal resistance is a growing concern.

Purpose of the Study:

• To identify and characterize Lomentospora prolificans isolates from Mexican patients.
• To determine the in vitro antifungal susceptibility of these isolates.
• To evaluate the pathogenicity of Lomentospora prolificans in a murine model.

Main Methods:

• Phenotypic and molecular identification (ITS rDNA sequencing) of 11 Lomentospora prolificans isolates.
• In vitro antifungal susceptibility testing against amphotericin B, fluconazole, voriconazole, posaconazole, and echinocandins using CLSI guidelines.
• Induction of systemic infection in ICR mice using three selected isolates to assess survival and fungal tissue burden.

Main Results:

• All 11 Lomentospora prolificans isolates exhibited resistance to all tested antifungal agents, including amphotericin B, azoles, and echinocandins.
• Significant mortality rates were observed in infected mice (100%, 90%, and 60% for strains 07-2239, 11-2242, and 04-2673, respectively).
• The highest fungal burden was consistently found in the brain, followed by the spleen and kidneys of infected mice.

Conclusions:

• Lomentospora prolificans isolates from Mexico demonstrate pan-resistance to currently available antifungal drugs.
• The fungus is pathogenic in a murine model, causing high mortality and disseminating to vital organs, particularly the brain.
• These findings underscore the critical need for developing novel therapeutic strategies to combat Lomentospora prolificans infections.