Fungi that are friendly to their hosts make themselves known

Microscopic image highlights the polymorphic nature of commensal C. albicans fungi, which are capable of growth in long filamentous and smaller yeast morphologies. Credit: Cincinnati Children’s

The discovery that our intestines contain a diverse community of often hazardous microorganisms sparked years of discussion over how we were forced to coexist with the enemy. For commensal populations of the yeast Candida albicans, the dreaded invader may be better considered as a friendly friend who has arrived bearing presents.

A team lead by Cincinnati Children’s infectious diseases expert Dr. Sing Sing Way, MD, Ph.D. published their findings in Cell Reports on May 17, 2022, with that finding as their primary takeaway.

“If this fungus chose to, it could make itself invisible to our bodies. Many of the mechanisms in which our immune system recognises it are obscured by it “The way I see it, anyway. Rather, our research demonstrates that it deliberately exposes itself to get the benefit of human bodies recognising and not attacking it.

It is common knowledge that probiotics, also known as “good” bacteria, can be beneficial to one’s health. Science has discovered that fungi can benefit humans in a variety of ways, including by performing comparable duties to bacteria in the commensal state.

While bacteria have been examined extensively, fungi have been under-researched compared to bacteria, Way explains.

Blinking ‘Hello’

Nowadays, scientists are more confident that a healthy balance of microbiota may be achieved by simply having specific fungus in the gut. It was possible to detect even inert fungus through their cell walls’ surface textures and chemical compositions.

“To provide the commensal benefit, this study indicates that commensal fungi must be alive and actively producing proteins that excite human immune cells. Because of their metabolic and transcriptional activity, they are required “As the saying goes, the only way is up.

As a first author, Tzu-Yu Shao collaborated with scientists from the University of California in San Francisco, the Institut Pasteur, and Cincinnati Children’s Hospital Medical Center to study how C. albicans is recognised as a commensal in mice.

An important gene in filamentation, UME6, is required for the “priming” of the intestinal C. albicans immune system, allowing it to fight against a wide spectrum of pathogens. Initially, the scientists thought that the priming effect would be induced by either extraordinarily high or low expression of this gene..

However, when C. albicans colonisation was restricted to one of two extremes, no positive effects were observed. As a result, designing the fungus so that UME6 expression oscillated between high and low was critical. C. albicans appears to send a signal to the body that it is advantageous by blinking back and forth. C. albicans is one of a number of microorganisms that the fungi aid the body fight off in exchange for not being chased out of the intestine.

“Human research revealed that the fungus must be alive in order to be detectable by our bodies. Clearly, they are acting in our best interests as well as their own: “As the saying goes, the only way is up.

What’s next?

Manipulating the growth of commensal fungus in the gut may be achievable in the future. As a first step, Way’s team is trying to figure out how this symbiotic relationship functions.

Fungal colonisation can begin immediately after birth, but it can take months for the process to be completed. Later, additional fungal populations may dive as a result of numerous occurrences. What effect do these variations in the population have on the commensal benefit? Furthermore, the researchers aim to investigate how commensal C. albicans affects other tissues, including the oral mucosa, lungs and the birth canal.

Way says, “We’re interested in figuring out in more depth how and why we are colonised with these bacteria.”. Additional next steps include understanding why colonisation does not generally produce abnormal inflammatory reactions given that our immune systems can identify them.

Further information: Tzu-Yu Shao et al, Candida albicans oscillating UME6 expression during intestinal colonization primes systemic Th17 protective immunity, Cell Reports (2022). DOI: 10.1016/j.celrep.2022.110837

Journal information: Cell Reports

Source: Cincinnati Children’s Hospital Medical Center