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Trichophyton rubrum DNA Strains in Patients with Onychomycosis with Persistent Mixed Infections Involving a Nondermatophyte Mold

Aditya K. Gupta MD, PhD, FRCP(C) and Kerry-Ann Nakrieko PhD
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Background

Onychomycosis is estimated to occur in approximately 10% of the global population, with most cases caused by Trichophyton rubrum. Some persistent onychomycosis is caused by mixed infections of T rubrum and one or more co-infecting nondermatophyte molds (NDMs). In onychomycosis, T rubrum strain types may naturally switch and may also be triggered to switch in response to antifungal therapy. T rubrum strain types in mixed infections of onychomycosis have not been characterized.

Methods

T rubrum DNA strains in mixed infections of onychomycosis containing co-infecting NDMs were compared with a baseline North American population through polymerase chain reaction amplification of ribosomal DNA tandemly repetitive subelements (TRSs) 1 and 2. The baseline DNA strain types were determined from 102 clinical isolates of T rubrum. The T rubrum DNA strain types from mixed infections were determined from 63 repeated toenail samples from 15 patients.

Results

Two unique TRS-2 types among the clinical isolates contributed to four unique TRS-1 and TRS-2 strain types. Six TRS-1 and TRS-2 strain types represented 92% of the clinical isolates of T rubrum. Four TRS-1 and TRS-2 strain types accounted for 100% of the T rubrum within mixed infections.

Conclusions

Four unique North American T rubrum strains were identified. In support of a shared ancestry, the T rubrum DNA strain types found in mixed infections with NDMs were among the most abundant types. A population of T rubrum strains in mixed infections of onychomycosis has been characterized, with more than one strain detected in some nails. The presence of a co-infecting NDM in mixed infections may contribute to failed therapy by stabilizing the T rubrum strain type, possibly preventing the antifungal therapy–induced strain type switching observed with infections caused by T rubrum alone.

Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.

Mycology Section, Mediprobe Research Inc, London, ON, Canada.

Corresponding author: Aditya K. Gupta, MD, PhD, FRCP(C), Mediprobe Research Inc, 645 Windermere Rd, London, ON, Canada N5X 2P1. (E-mail: agupta@mediproberesearch.com)