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Published on: September 16, 2022
Sodium lignosulfonate causes cell membrane perturbation in the human fungal pathogen Candida albicans
1Department of Biotechnology, National Institute of Technology Raipur, Raipur, 492010, Chhattisgarh, India.
Abstract:
Underestimating fungal infections led to a gap in the development of antifungal medication. However, rising rates of morbidity and mortality with fungal infection have revealed an alarming rise in antifungal resistance also. Due to the eukaryotic properties of fungi and the close evolutionary similarity between fungal cells and human hosts, therapeutic targeting of Candida infections is troublesome, along with the development of resistance. The discovery of new antifungals is so far behind schedule that the antifungal pipeline is nearly empty. Previously, we have reported the activity and susceptibility of Sodium lignosulfonate (LIG) against C. albicans. In this work, we have established the mechanistic actions of LIG's activity. We performed flow cytometric analysis for membrane integrity, ergosterol binding assay, crystal violet assay, and membrane leakage assay to analyze quantitatively that the C. albicans membrane is being disrupted in response to LIG. Electron microscopic analysis with SEM and TEM confirmed changes in Candida cellular morphology and membrane perturbation respectively. These findings indicated that LIG causes cell membrane damage in C. albicans. This knowledge about LIG's mechanism of action against C. albicans could be used to explore it further as a lead antifungal molecule to develop it as a potent candidate for antifungal therapeutics in the future.
Insights
Sodium lignosulfonate (LIG) disrupts the cell membrane of Candida albicans, offering a potential new avenue for antifungal drug development against resistant fungal infections.
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Rising antifungal resistance and mortality underscore the urgent need for novel antifungal therapies.
- Targeting Candida infections is challenging due to similarities between fungal and human cells, complicating drug development.
- The antifungal drug pipeline is critically depleted, necessitating exploration of new therapeutic agents.
Purpose of the Study:
- To elucidate the mechanistic actions of Sodium lignosulfonate (LIG) against Candida albicans.
- To investigate LIG's potential as a lead antifungal molecule.
Main Methods:
- Quantitative analysis using flow cytometry for membrane integrity and membrane leakage assays.
- Ergosterol binding and crystal violet assays were employed to assess LIG's impact.
- Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to visualize cellular and membrane changes.
Main Results:
- LIG was confirmed to disrupt the cell membrane integrity of Candida albicans.
- Analysis indicated significant membrane perturbation and damage in response to LIG treatment.
- Microscopic analysis revealed alterations in Candida cellular morphology and membrane structure.
Conclusions:
- Sodium lignosulfonate (LIG) exerts its antifungal activity by causing direct damage to the Candida albicans cell membrane.
- Understanding LIG's mechanism provides a foundation for its future development as a potent antifungal therapeutic candidate.
