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

Abstract

BACKGROUND:Onychomycosis is estimated at approximately 10% of the global population with most cases caused by Trichophyton rubrum (T. rubrum). Some of the persistent cases of onychomycosis are caused by mixed infections of T. rubrum and one or more co-infecting nondermtophyte mould (NDM). T. rubrum strain types in onychomycosis may naturally switch and may also be triggered to switch as a 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 NDM(s) were compared to a baseline North American population through polymerase chain reaction amplification of ribosomal DNA tandemly repetitive subelement one and two (TRS1 and TRS2). The baseline strain types consisted of 102 clinical isolates of T. rubrum from onychomycosis patients and the patients with mixed infections of T. rubrum and an NDM(s) consisted of 63 repeat toenail samples from 15 onychomycosis patients with mixed infections of T. rubrum and an NDM(s). RESULTS:Two unique TRS2-types among the clinical isolates contributed to four unique TRS1;TRS2 strain types. Six TRS1;TRS2 strain types represented 92% of the clinical isolates of T. rubrum. Four TRS1;TRS2 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 within 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 antifungal therapy-induced strain type switching observed with infections caused by T. rubrum alone.

Anti-dermatophytic activity of cold atmospheric plasma against Trichophyton rubrum via affecting fungal growth, morphology, drug susceptibility and HSP90 gene expression

“…Due to the nature of T. rubrum infections which is comprised of a complex mixture of species 31 , 32 , the generalizability of this study is somehow limited, nevertheless due to the extreme genotypic similarity 33 the observed results could be expanded to other species. Several questions remained unanswered about the reactive species and the precise influence of CAP irradiation on various critical virulence factors, gene regulatory elements, and membrane determinants.…”

A Practical Guide to Curing Onychomycosis: How to Maximize Cure at the Patient, Organism, Treatment, and Environmental Level

“…For instance, strain A of T. rubrum was found to be the most prevalent strain in Europe, whereas T. rubrum strain D is more common in North America (38% and 26%, respectively) [66,67]. Strain type switching can occur naturally as well but can also be influenced by the presence of antifungal therapy and mixed infections [66,68]. The reduction in strain type switching observed in mixed infections may contribute to failed therapy in mixed infection compared to dermatophyte-only infections.…”

“…This may be linked to an enhanced cell-mediated immunity observed with successful terbinafine therapy [69]. Molecular-based techniques such as polymerase chain reaction (PCR) amplification can allow strain type to be identified; strain type identification cannot be determined through culturing [68,70]. The presence of mixed infections may also impact strain type switching [68].…”

“…Molecular-based techniques such as polymerase chain reaction (PCR) amplification can allow strain type to be identified; strain type identification cannot be determined through culturing [68,70]. The presence of mixed infections may also impact strain type switching [68]. Mixed infections may be more prevalent than previously thought [68].…”

“…The presence of mixed infections may also impact strain type switching [68]. Mixed infections may be more prevalent than previously thought [68]. Despite the broad-spectrum activities of most antifungal therapies, mixed infections [e.g., dermatophyte and non-dermatophyte molds (NDMs)] may present treatment difficulties [31,71,72].…”