Date Published: April 4, 2019
Publisher: Public Library of Science
Author(s): Bibekananda Kar, Pavan Patel, Stephen J. Free, Katherine A. Borkovich.
The Trichophyton rubrum genome contains six proteins containing two or more lysin M (LysM) domains. We have characterized two of these proteins, LysM1 and LysM2, and demonstrated that these proteins have the capacity to bind two substrates, chitin and N-linked oligosaccharides associated with human skin glycoproteins. We have characterized the individual LysM domains in LysM1, and shown that the protein contains two functional LysM domains. Each of these domains can bind to chitin, to N-linked oligosaccharides in human skin glycoproteins, and to N-linked oligosaccharides on fungal glycoproteins. We hypothesize that LysM proteins could provide the pathogen with three important functions. First, the T. rubrum LysM proteins could shield host cell wall chitin from the human immune system. Second, the LysM proteins could shield the pathogen’s glycoproteins from host degradation and immune surveillance. Third, the LysM proteins could help facilitate pathogen adhesion to human skin.
Human-pathogenic dermatophytes exclusively infect keratinized tissues of human skin, nails, and hair . Unlike fungal infections caused by opportunistic fungi in compromised hosts, the dermatophytes are obligate animal pathogens and infect healthy hosts. Dermatophytes seldom colonize beyond the epidermis. However, in patients with a CARD9 deficiency dermatophytes, have been reported to cause subcutaneous infections and to spread to the lymph nodes . Superficial dermatophyte infections are very common, and 10–20% of the worldwide human population suffer from dermatophyte infections . These infections are often very difficult to treat and have a high frequency of reoccurrence . Trichophyton rubrum is the most common fungal dermatophyte and is known to account for 60% of all clinical dermatophyte infections. The fungus causes a variety of chronic skin infections including toenail infections (onychomycosis) athlete’s foot (tinea pedis), ringworm (tinea capitis), and jock itch (tinea cruris).
LysM proteins are carbohydrate-binding proteins that have been found in bacteriophages, bacteria, fungi, plants, and animals. LysM proteins have been shown to bind to N-acetylglucosamine-containing oligosaccharides, including bacterial cell wall peptidoglycans and chitin. LysM motifs are found in a variety of proteins and are thought to function in allowing these proteins to specifically recognize and bind to glycans. The recent sequencing of the T. rubrum genome showed that the genome contained fifteen LysM domain proteins, while related nonpathogens contained between zero and four such proteins . The increase in LysM proteins encoded in the T. rubrum genome suggests that these proteins may be important for the pathology of the fungus. Three of these proteins had a LysM domain and a chitinase domain, suggesting the encoded proteins functioned as chitinases. Six of the LysM domain proteins contained multiple LysM domains, and no obvious homologies to other proteins.