Indole propionic acid induced Ca²⁺‐dependent apoptosis in Candida albicans

Abstract

Indole propionic acid (IPA) which majorly influences the modulation of cellular respiration is a metabolite generated by gut microbiota. The antimicrobial effects of IPA have not been previously demonstrated. Therefore, this study focused on investigating the antimicrobial activity of IPA. Initially, antifungal activity of IPA against Candida albicans was observed, accompanied by variations in mitochondrial respiration indicating modulation of NAD+/NADH ratios. Consumption of O2 contributes to the respiratory regulation and triggered by Ca2+ overloading. After treatment with IPA, the cells were monitored, and Ca2+ increases leading to membrane depolarization and reactive oxygen species (ROS) accumulation in mitochondria were noted. Depolarization of mitochondria membrane induced release of proapoptotic proteins in mitochondria. Oxidative stress exerted by ROS contributed to glutathione depletion and oxidation of glutathione (GSH). Fragmentation of DNA is a characteristic event leading to apoptosis and accompanies major hallmarks of apoptosis including phosphatidylserine exposure and metacaspase activation. In addition, phosphatidylserine exposure and metacaspase activation were detected in the cell treated with IPA. In conclusion, IPA triggered apoptosis in C. albicans under the influence of Ca2+.

Microbe-Drug Association Prediction Model Based on Graph Convolution and Attention Networks

“…Furthermore, in the antimicrobial treatment of aggressive infections caused by Morganella morganii, Radica Zivkovic 3, our model also identified other drugs with antimicrobial effects against Candida albicans. For example, Giyeol Han [26] et al discovered that indole-3-acetic acid could induce apoptosis in Candida albicans under the influence of Ca 2+ , as confirmed in the table with PMID 34779568. Additionally, Sivaraman Dhanasekaran [27] et al explored phytotherapy to discover new antifungal agents like Hesperidin.…”

Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

“…Importantly, after IPA treatment, the bacterial load in the lungs of mice infected with M. tuberculosis aerosol decreased without adverse reactions. IPA not only shows antibacterial activity against some clinically resistant M. tuberculosis and non- Mycobacterium tuberculosis (NTM) species, but also induces programmed cell death of Candida albicans dependent on Ca 2+ [ 135 ] ( Table 2 ). However, under experimental conditions, IPA has no antibacterial activity against some Gram-positive bacteria ( Staphylococcus aureus ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aeruginosa , and Acinetobacter baumannii ) [ 133 , 134 ].…”