Hypochlorous acid, commonly known as bleach, generated during the immune response of a cell is a potent killing agent against a common fungal pathogen, Candida albicans.
The laboratory finding, highlighted in a paper published in the coming issue of mBio, also uncovers some of hypochlorous acid’s (HOCI) mechanisms of actions in that killing process.
The work could be a significant step toward using HOCI as a novel therapeutic strategy against C. albicans, and potentially other pathogens.
C. albicans causes infection worldwide. It is particularly virulent in immunocompromised patients and the cause of dangerous systemic infections in this population. There have been many effective treatments against the fungal pathogen, but for decades drug resistance has been problematic when treating infections cause by C. albicans.
Most studies looking at this immune response against the fungal pathogen have focused on hydrogen peroxide (H2O2), not HOCI. Phagocytes capture the fungal invader and in the process two oxidants are created—H202 and HOCI. Myeloperoxidase converts H2O2 created during the oxidative burst in the phagosome into HOCI, the more potent killing agent.
“We discovered that hypochlorous acid kills cells by targeting the plasma membrane and oxidizing cellular components in a very different way than hydrogen peroxide,” says James Konopka, lead author and professor in the microbiology and immunology department in the Renaissance School of Medicine at Stony Brook University.
“It disrupts the C. albicans plasma membrane, produces a very different transcriptional response than hydrogen peroxide, is more effective and disruptive to the plasma membrane, and therefore has a more distinct effect on killing these fungal cells.”
Konopka explains that neutrophils are the critical cell type for controlling infections by C. albicans and other fungal pathogens. They are distinct because they make high levels of myeloperoxidase compared to other phagocytes, such as macrophages. This study shows the important aspect of the neutrophil response, essential to the oxidative process that produces this fungal killing HOCI or bleach.
While the laboratory results will not have any immediate impact on new treatments against C. albicans infections, Konopka believes the findings provide a basis for designing new therapeutic strategies against this pathogen that causes infections worldwide.
Researchers at Seoul National University in South Korea also contributed to the work.
A grant from the National Institutes of Health’s Institute of Allergies and Infectious Disease supported the research.
Source: Stony Brook University
