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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Mechanism underlying renal failure caused by pathogenic Candida albicans infection
Shin Jae-Chen1, Jeon Young-Joo2, Park Seon-Min1
1Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongbuk, Republic of Korea.
Abstract:
Candida albicans (C. albicans) is an opportunistic fungal pathogen that commonly causes nosocomial infections. Systemic candidiasis is encountered with increasing frequency in immunocompromised hosts, leading to renal failure that results in severe morbidity and mortality. The present study investigated the mechanisms underlying kidney susceptibility following infection with several C. albicans strains, such as B311 and SC5314. Fungal growth of the highly virulent SC5314 strain was 103-fold higher compared to the nonpathogenic B311 strain in the kidneys. An intravenous challenge of SC5314 in mice, elevated blood urea nitrogen (BUN) and creatine levels, which resulted in mortality at 8 or 35 days after infection in a dose- and time-dependent manner, whereas all the B311-infected mice had BUN and creatinine levels in the normal range and survived. Whether virulent C. albicans may escape clearance by activating signaling pathways that lead to the production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was investigated. B311 infections significantly elevated TNF-α and IL-1β mRNA expression in the kidneys, whereas the expression in SC5314-infected mice remained unchanged. Furthermore, B311 infection significantly elevated the plasma levels of TNF-α and IL-1β. These results indicated that the less virulent strains of C. albicans induced pro-inflammatory cytokines in mice. These results determined that an impairment of the protective mechanisms occurred in the kidneys with virulent C. albicans infection.
Insights
Virulent Candida albicans strains impair kidney protective mechanisms, leading to renal failure and mortality in immunocompromised hosts. Less virulent strains, however, trigger protective pro-inflammatory cytokine responses.
Area of Science:
- Mycology
- Immunology
- Pathogenesis
Background:
- Candida albicans is an opportunistic fungal pathogen causing nosocomial infections.
- Systemic candidiasis in immunocompromised individuals frequently leads to severe renal failure, morbidity, and mortality.
Purpose of the Study:
- To investigate the mechanisms of kidney susceptibility to C. albicans infection.
- To compare the pathogenic potential of different C. albicans strains in murine kidneys.
- To explore the role of pro-inflammatory cytokines in C. albicans-induced kidney injury.
Main Methods:
- Intravenous challenge of mice with virulent (SC5314) and nonpathogenic (B311) C. albicans strains.
- Quantification of fungal growth in kidneys.
- Measurement of blood urea nitrogen (BUN) and creatinine levels.
- Assessment of TNF-α and IL-1β mRNA expression and plasma levels.
Main Results:
- The highly virulent SC5314 strain exhibited 10^3-fold higher fungal growth in kidneys compared to the nonpathogenic B311 strain.
- SC5314 infection led to elevated BUN and creatinine levels and dose-/time-dependent mortality, while B311 infection did not affect these parameters.
- B311 infection significantly upregulated kidney TNF-α and IL-1β mRNA expression and plasma levels, whereas SC5314 infection did not.
Conclusions:
- Less virulent C. albicans strains induce pro-inflammatory cytokine production, suggesting a protective immune response.
- Virulent C. albicans strains impair these protective mechanisms, leading to kidney susceptibility and severe outcomes.
- Understanding these differential responses is crucial for managing systemic candidiasis in vulnerable populations.
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