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Published on: September 21, 2019
Experimental murine model of disseminated Pseudallescheria infection
G M González1, R Tijerina, L Najvar
1The University of Texas Health Science Center at San Antonio, Department of Medicine, 78229-3900, USA. gmglez@yahoo.com.mx
Abstract:
Pseudallescheria boydii is found in soil and has a worldwide distribution. This fungus was initially identified as a pathogen targeting a variety of tissues. There are fragmentary data in the literature on the in vitro susceptibility of P. boydii to different antifungal compounds. P. boydii is highly refractory to antifungal treatments. In this study, a murine model of disseminated Pseudallescheria infection was developed to evaluate efficacy of different treatment regimens. A clinical strain of P. boydii was studied in normal and neutropenic outbred ICR mice. Several inocula were tested over a range from 1 x 10(3) to 5 x 10(6) cfu. Groups of eight mice were injected with a intravenous dose of one inoculum. Mortality correlated with the dose of the inoculum, and with immunosuppression. Quantitative cultures of various tissues showed initial dissemination of disease in immune competent mice. This was followed by, reduction of tissue burden, except in the brain. In contrast, disseminated infection persisted in most organs in immunosuppressed animals (p < 0.0001). This model should be appropriate for in vivo evaluation of antifungal chemotherapy.
Insights
Pseudallescheria boydii infections are difficult to treat. A new mouse model shows infection severity depends on fungal dose and host immune status, aiding antifungal drug evaluation.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Pseudallescheria boydii is a soil fungus with global distribution, recognized as a pathogen.
- Limited data exists on its susceptibility to antifungal agents, and it is known for treatment resistance.
- Invasive P. boydii infections pose significant clinical challenges due to high antifungal refractoriness.
Purpose of the Study:
- To develop and validate a murine model for disseminated Pseudallescheria infection.
- To assess the impact of fungal inoculum dose and host immunosuppression on infection progression.
- To establish a platform for evaluating antifungal chemotherapy efficacy in vivo.
Main Methods:
- A clinical isolate of Pseudallescheria boydii was used to infect outbred ICR mice.
- Mice were either normal or rendered neutropenic (immunosuppressed).
- Intravenous inoculation with varying fungal concentrations (1 x 10(3) to 5 x 10(6) CFU) was performed, followed by mortality assessment and quantitative tissue cultures.
Main Results:
- Mortality rates directly correlated with the administered fungal inoculum dose.
- Immunosuppression significantly exacerbated infection persistence across multiple organs (p < 0.0001).
- In immunocompetent mice, initial dissemination was followed by fungal burden reduction, except in the brain, while immunosuppressed mice showed persistent infection.
Conclusions:
- The developed murine model accurately reflects disseminated Pseudallescheria infection dynamics.
- Host immune status critically influences infection outcome and fungal burden.
- This model is suitable for the in vivo assessment of novel antifungal treatments against P. boydii.
