It makes me itchy just thinking about it: the genomes of seven skin-infecting fungi have revealed some surprising facts about these common but little-understood pathogens. The results, published in mBio this week, show these 7 dermatophytes all have one surprising feature that could help explain why athlete’s foot and other fungal skin infections are so very difficult to treat. And why they keep coming back after they’ve apparently been wiped out.
Dermatophytes cause some of the most common infections around, but since they seldom kill you, they don’t get the attention more virulent and demonstrative microbes enjoy (I’m looking at you, Ebola). We have dozens of complete genome sequences for fungal pathogens like Candida albicans, but until now not one athlete’s foot isolate - Trichophyton rubrum - had been sequenced.
Christina Cuomo of the Broad Institute co-authored the paper. She says athlete’s foot, like other dermatophytes, may not register as a global threat, but it does cause a great deal of distress, partly because of it’s tendency to re-occur.
“They’re infections that are difficult to treat and resolve. A lot of people carry T. rubrum as a commensal, and, as many people know, it’s difficult to get rid of completely – it can be an ongoing infective cycle,” says Cuomo.
The study in mBio adds to what we know about dermatophytes with genomes for T. rubrum, T. tonsurans (ringworm of the scalp), T. equinum (causes a skin condition in horses), Microsporum canis (again, causes scalp ringworm and a similar condition in pets) and M. gypseum (which causes skin or scalp lesions).
Genomes reveal common threads among dermatophytes
With these seven genomes in hand, the authors set out to find what makes dermatophytes tick. Co-author Theodore White of University of Missouri-Kansas City says that, compared to other fungi, dermatophytes are enriched in four kinds of enzymes: skin-degrading enzymes (seems predictable), kinases (which may be involved in signaling), secondary metabolites (that may well suppress the immune system or degrade and kill skin cells), and a surprise set of enzymes that are rich with LysM domains.
These LysM domains, says White, are the most interesting discovery as far as he is concerned.
What are LysM domains doing in dermatophytes?
LysM domains were originally found in bacteria, he says, where they bind and degrade sugars in bacterial cell walls. They’re found in fungal plant pathogens as well, where other researchers have hypothesized the LysM domains bind chitin – a carbohydrate polymer in fungal cell walls – in the pathogen’s own cell walls to mask itself from the plant’s defenses. “Like the candy coating shell on an M&M,” says White.
White says LysM domains are present in many medically important fungi, but not to the extent they are found in these dermatophytes. He says dermatophytes may well use LysM to bind chitin during infection, allowing the fungus to hide in plain sight, evading the human immune system and allowing the pathogen to re-emerge when the conditions are right.
“Dermatophytes have a strange relationship with the human immune system. When you get athlete’s foot on and off, have you eliminated the dermatophytes, or are they still hanging out on your feet waiting, or is the recurrence due to re-infection? The genome sequences will help us answer those questions.” LysM may be a key to unlocking the strange relationship, according to White, and he expects the genome sequences that he and his colleagues have published this week will spur more questions about LysM and about how it can be targeted with therapies and preventatives.