The human gut microbiome contains a wide range of organisms, including different bacteria, viruses, and fungi, including the fungus Candida albicans. This natural fungus has two different forms, one of which is a round yeast cell that is harmless, while the other grows extensions that care known as hyphae. The hyphal form of C. albicans can cause mild to severe illness in people, and can also release a toxin called candidalysin, which seems to have a central role in those infections. Researchers have now found that the candidalysin toxin can also have a significant influence on how microbes grow in the gastrointestinal tract. The findings have been reported in Nature.
Previous research has suggested that the round-cell form of Candida albicans yeast can be a beneficial influence on the colonization of the intestine by microbes, noted Professor Bernhard Hube of the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI). But the hyphal form of Candida releases candidalysin, which damages cells and has been thought to be primarily pathogenic.
The researchers wanted to know more about why so many isolates of C. albicans can grow hyphae, and why the beneficial, round form of healthy C. albicans retains the ability to grow those dangerous hyphae and release a toxic molecule.
With a mouse model, the researchers have now challenged the idea that the round form of C. albicans is better for promoting microbial colonization in the gut. They determined that when a complex community of bacteria is already in place, C. albicans can exist in both the round and hyphae forms to promote the efficient growth of gut microbes.
The toxin candidalysin is only generated by the hyphal form of the fungus, which exerts an antibacterial effect. The hyphal fungus is then able to compete with the gut bacteria; the candidalysin toxin disrupts the multiplication of bacteria to give the fungus a competitive edge, and serve as a check on bacterial growth. The gut is also able to tamp down the growth of C. albicans; the researchers determined that immunoglobulin A in the intestine can disrupt the yeast.
"The release of candidalysin associated with the formation of hyphae therefore probably contributes to the fact that the fungus is such a successful colonizer of humans. This may explain why the hyphal form of C. albicans is also so important during colonization of the intestine," said Hube. When hyphae formation is blocked, the ability of the fungus to colonize the intestine is also impaired.
"The fungus has therefore not developed the toxin primarily to damage human cells, but to be able to compete with bacteria on mucous membranes," Hube suggested.
Sources: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (Leibniz-HKI), Nature
