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Updated: Aug 7, 2026
A Catheter-Related Candida albicans Infection Model in Mouse
Published on: March 22, 2024
Cardiac failure in C5-deficient A/J mice after Candida albicans infection
Alaka Mullick1, Zully Leon, Gundula Min-Oo
1Biotechnology Research Institute, National Research Council, 6100 Royalmount Avenue, Montréal, Québec, Canada H4P 2R2. alaka.mullick@cnrc-nrc.gc.ca
Abstract:
The effect of a deficiency in the C5 component of complement on the pathophyisology of infection with the fungal pathogen Candida albicans was studied by using the A/J inbred mouse strain and the BcA17 congenic mouse strain. Acute infection caused by intravenous injection of C. albicans blastospores is associated with rapid fungal replication in the heart, brain, and, in particular, kidneys of C5-deficient mice. Histological studies and analysis of markers for tissue damage indicated that the heart is the organ that is most affected and that it ultimately fails in C5-deficient mice. In A/J and BcA17 mice, tissue damage is associated with (i) cellular infiltration in the heart, which is not seen in the kidney despite the higher fungal load in the latter organ, and (ii) a very strong inflammatory response, including elevated levels of many cytokines and chemokines. This results in cardiomyopathy, which is associated with elevated levels of creatine kinase and cardiac troponin I in the circulation. Damage to the cardiac muscle is associated with metabolic changes, including hypoglycemia, decreased lipid utilization resulting in elevated levels of cardiac triglycerides, and unproductive glucose utilization linked to a dramatic increase in the level of pyruvate dehydrogenase kinase 4 (Pdk4), a negative regulator of the pyruvate dehydrogenase complex.
Insights
Complement C5 deficiency severely impacts Candida albicans infection, causing heart failure in mice. This deficiency leads to rapid fungal growth and significant cardiac damage due to inflammation and metabolic changes.
Area of Science:
- Immunology
- Mycology
- Pathophysiology
Background:
- The complement system, particularly the C5 component, plays a crucial role in host defense against pathogens.
- Candida albicans is an opportunistic fungal pathogen that can cause severe systemic infections.
Purpose of the Study:
- To investigate the role of complement component C5 deficiency in the pathophysiology of Candida albicans infection.
- To elucidate the mechanisms underlying tissue damage and organ failure in C5-deficient mice during candidiasis.
Main Methods:
- Utilized A/J and BcA17 congenic mouse strains to model C5 deficiency.
- Administered C. albicans blastospores intravenously to induce acute infection.
- Performed histological analysis and measured tissue damage markers.
- Assessed levels of cytokines, chemokines, cardiac enzymes, and metabolic regulators.
Main Results:
- C5-deficient mice exhibited rapid fungal replication in the heart, brain, and kidneys.
- The heart was the most severely affected organ, leading to cardiac failure.
- Tissue damage in C5-deficient mice was characterized by cardiac cellular infiltration and a strong inflammatory response.
- Elevated levels of creatine kinase, cardiac troponin I, and pyruvate dehydrogenase kinase 4 (Pdk4) were observed, indicating cardiac muscle damage and metabolic dysregulation.
Conclusions:
- Complement C5 is essential for controlling Candida albicans infection and preventing severe organ damage.
- C5 deficiency leads to uncontrolled fungal growth, inflammation-driven cardiomyopathy, and metabolic disturbances.
- Targeting complement C5 or modulating inflammatory and metabolic pathways may offer therapeutic strategies for invasive candidiasis.
