Our bodies host a variety of microorganisms, and the microbial communities in and on our bodies have to maintain the right balances among their members, or problems can arise. This includes the overgrowth of harmful species, which are typically kept in check by the growth of other, beneficial microbial species. Candida albicans is a fungus that is a normal part of the human microbiome, for example, but it can cause problems when too much of it grows. Recent studies have found that even though Candida albicans is a normal part of the microbiome of roughly 50% of all people, the fungus is also responsible for about 70% of problematic fungal infections, worldwide.
Now scientists have revealed a novel mechanism that Candida albicans uses to damage tissue. This process involves a human protein called albumin, and it may explain why some strains of Candida albicans seem harmless when they are analyzed in a laboratory, but they cause serious infections in people. The findings have been reported in Nature Communications.
Candida albicans is known to grow processes called hyphae that can invade the tissues of its host, and produce toxins that cause problems. This latest work has shown how crafty this organism is, and the many ways it can damage human tissue.
When scientists have examined Candida albicans that has been isolated from patient infections, some haven't caused problems when applied to laboratory research models. This led scientists to wonder what they were missing.
A protein known as albumin is the most common blood protein in humans, and has a variety of important roles. But it seems albumin can also be hijacked. When Candida was grown in the presence of albumin, even strains that are not pathogenic become invasive and dangerous: they grow tough colonies known as biofilms; and they started producing a molecule called 13-HODE that can harm human cells
"Even strains or mutants previously considered non-virulent in the lab became cytotoxic when albumin was present," said first study author Sophia Hitzler, a graduate candidate in the lab of Mark Gresnigt at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI). "We discovered that Candida albicans can use an alternative pathogenicity strategy."
This work has highlighted the adaptability of pathogens, and has also revealed considerations that should be applied to future research on fungal pathogens. Namely, are host cell proteins contributing to the mechanisms of these pathogens? Model systems that investigate such questions should reflect the human host environment as accurately as possible.
"Just providing essential nutrients in the lab is not enough," Hitzler noted. "You need the right environmental cues. Otherwise, you might overlook strains that are actually dangerous in the human body."
While this work has shown that Candida albicans is an adaptable pathogen that can take advantage of host cell proteins, it also revealed another protein that the infection relies on, and could make it vulnerable.
Sources: Leibniz Institute for Natural Product Research and Infection Biology, Nature Communications
