Candida albicans (a fungus) is fought by Vitamin D in many ways – Sept 2022

Antifungal activity of vitamin D 3 against Candida albicans in vitro and in vivo

Microbiol Res. 2022 Sep 20;265:127200. doi: 10.1016/j.micres.2022.127200 FREE PDF below
Junwen Lei 1 , Wei Xiao 2 , Jinping Zhang 3 , Fangyan Liu 4 , Caiyan Xin 5 , Bo Zhou 6 , Wenbi Chen 7 , Zhangyong Song 8

The incidence of intra-abdominal candidiasis (IAC), characterized by high morbidity and mortality, has become a serious concern. The limitations of current antifungal drugs on the market underscores the importance of the development of novel antifungal agents. In the present study, the antifungal activity of vitamin D3 (VD3) against various Candida species was investigated.

In vitro, the broth microdilution method and solid plate assay confirmed that VD3 inhibited the growth of Candida spp. in a broad-spectrum, dose-dependent manner.
VD3 also had a significant antifungal effect on the

  • initiation,
  • development, and
  • maturation phases

of biofilm formation in Candida albicans.
The mechanism of VD3 action was explored by transcriptomics and reverse transcription quantitative PCR (RT-qPCR) analysis, and showed that VD3 affects

  • ribosome biogenesis,
  • coenzyme metabolism, and
  • carbon metabolism.

These results suggested that VD3 may have multitarget effects against C. albicans.
In the murine IAC model, VD3 reduced the fungal burden in the liver, kidneys, and small intestine. Further histopathological analysis and quantification of plasma cytokine levels confirmed that VD3 treatment significantly decreased the infiltration of inflammatory cells and the levels of plasma interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Taken together, these findings suggest a new antifungal mechanism for VD3 and indicate that VD3 could be an effective therapeutic agent for use in IAC treatment.
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Vitamin D3: A promising antifungal and antibiofilm agent against Candida species - June 2023

Curr Med Mycol . 2023 Jun;9(2):17-22. doi: 10.18502/cmm.2023.345062.1416.
Zahra Kherad 1, Somayeh Yazdanpanah 1, Farshid Saadat 2, Keyvan Pakshir 1 3, Kamiar Zomorodian 1 3

Background and purpose: Candida species are opportunistic fungal pathogens that cause mild to life-threatening infections in both immunocompetent and immunocompromised populations. The increasing prevalence of drug-resistant Candida species has posed a significant challenge to the management of infections in clinical settings. Therefore, this study aimed to investigate the direct antifungal and antibiofilm effect of vitamin D3 against Candida species.

Materials and methods: The antifungal activity of vitamin D3 was evaluated by broth microdilution method based on the Clinical and Laboratory Standard Institute. Prevention of biofilm formation by Candida albicans was measured using the XTT assay following exposure to different concentrations of vitamin D3. Moreover, expression of Agglutinin-like sequence gene 1 (ALS1), hyphal wall protein gene (HWP1), secreted aspartyl proteinase 6 gene (SAP6), and morphogenesis pathway regulatory gene (EFG1) were analyzed by real-time polymerase chain reaction using the comparative Ct method (ΔΔ Ct) after exposure to vitamin D3.

Results: Vitamin D3 showed antifungal activity against Candida species ranging from 1-128 μg/mL. Furthermore, vitamin D3 inhibited biofilm formation in a dose-dependent manner, with IC50 of 7.5 μg/mL. Treatment with vitamin D3 resulted in significant upregulation of the EFG1, ALS1, and SAP6 genes under hypha-inducing conditions to overcome environmental challenges.

Conclusion: Results of the current study demonstrated that vitamin D3 has a significant inhibitory effect on Candida growth and biofilm formation. Considering its demonstrated antifungal and antibiofilm properties, vitamin D3 holds promise as a potential agent for medical applications.
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A new study suggests that fungal infections now account for around 6% of global deaths - Jan 2024

The Telegraph

  • "Around four million people are dying every year from fungal infections, new research indicates – nearly double the previous global estimate."
  • "... killing six times more people than malaria, and almost three times as many as tuberculosis."

"Global incidence and mortality of severe fungal disease" Lancet Jan 2024 behind paywall https://doi.org/10.1016/S1473-3099(23)00692-8
Summary
Current estimates of fungal disease incidence and mortality are imprecise. Population at risk denominators were used to estimate annual incidence for 2019–21. Extensive literature searches from 2010 to 2023 were combined with over 85 papers on individual country and global disease burden. Crude and attributable mortality were estimated using a combination of untreated mortality, the proportion of patients who are treated, and percentage survival in treated patients. Awareness, guidelines, and accessibility of diagnostics and therapies informed the ratio of treated to untreated cases. Estimates do not include influenza or COVID-19 outbreaks.
Data from more than 120 countries were included.
Annually, over 2 113 000 people develop invasive aspergillosis in the context of chronic obstructive pulmonary disease, intensive care, lung cancer, or haematological malignancy, with a crude annual mortality of 1 801 000 (85·2%).
The annual incidence of chronic pulmonary aspergillosis is 1 837 272, with 340 000 (18·5%) deaths. About 1 565 000 people have a Candida bloodstream infection or invasive candidiasis each year, with 995 000 deaths (63·6%).
Pneumocystis pneumonia affects 505 000 people, with 214 000 deaths (42·4%).
Cryptococcal meningitis affects 194 000 people, with 147 000 deaths (75·8%).
Other major life-threatening fungal infections affect about 300 000 people, causing 161 000 deaths (53·7%).

Fungal asthma affects approximately 11·5 million people and might contribute to 46 000 asthma deaths annually. These updated estimates suggest an annual incidence of 6·5 million invasive fungal infections and 3·8 million deaths, of which about 2·5 million (68%; range 35–90) were directly attributable.

Google Scholar had 11,800 hits for "Candida albicans" and "Vitamin D" March 2024

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