<i>Trichophyton rubrum</i>DNA strain switching increases in patients with onychomycosis failing antifungal treatments

Gupta, AK; Nakrieko, Kerry-Ann

doi:10.1111/bjd.13165

Cited by 21 publications

(17 citation statements)

References 30 publications

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“…It is highly recommended that, if the first test is positive for an NDM, additional patient sampling be undertaken on a minimum of two separate occasions before initiating treatment, and direct microscopy examination be included in the full mycological evaluation, as recommended for confirmation of NDMs as etiological agents [5,19,20]. It is noteworthy that terbinafine resistance is rare in dermatophytes [21,22] and a logical explanation for apparently failed terbinafine treatments of dermatophyte infections could be the presence of a mixed dermatophyte-NDM infection.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of mixed infections in global onychomycosis

Gupta

Taborda²,

Taborda³

et al. 2020

PLoS ONE

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Onychomycosis is estimated at a prevalence of 10% worldwide with the infecting organism most commonly Trichophyton rubrum (T. rubrum). Traditional culture identification of causative organisms has inherent risks of overestimating dermatophytes, like T. rubrum, by inhibiting the growth of possible nondermatophyte mould (NDM) environmental contaminants which could be causative agents. Recently, molecular methods have revealed that a proportion of onychomycosis cases in North America may be caused by mixed infections of T. rubrum as an agent co-infecting with one or more NDM. Determining the global burden of mixed infections is a necessary step to evaluating the best therapies for this difficult-to-treat disease. To determine the prevalence of mixed infections in a global population, nail samples from onychomycosis patients in Brazil, Canada, and Israel (n = 216) were analyzed by molecular methods for the presence of dermatophytes and five NDMs. If an NDM was detected, repeat sampling was performed to confirm the NDM. T. rubrum was detected in 98% (211/216) of infections with 39% mixed (84/216). The infection type was more likely to be mixed in samples from Brazil, but more likely to be a dermatophyte in samples from Canada and Israel (Χ 2 = 16.92, df = 2, P<0.001). The most common cause of onychomycosis was T. rubrum. In all countries (Brazil, Canada and Israel combined) the prevalence of dermatophyte (Χ 2 = 211.15, df = 3, P<0.001) and mixed (dermatophyte and NDM; Χ 2 = 166.38, df = 3, P<0.001) infection increased with patient age. Our data suggest that mixed infection onychomycosis is more prevalent than previously reported with the aging population being at increased risk for mixed infections.

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Section: Discussionmentioning

confidence: 99%

High prevalence of mixed infections in global onychomycosis

Gupta

Taborda²,

Taborda³

et al. 2020

PLoS ONE

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“…First, strain typing of T. rubrum was performed by Southern blot hybridization based RFLP analysis, 17 the method used in the most recent study which found the strain switching in patients with onychomycosis. 18 Then, species-specific PCR primers targeting tandemly repetitive subelements in NTS (TRS-1, TRS-2) were synthesized to detect interspecies variations. Assays of TRS-1 and TRS-2 polymorphisms in 101 clinical isolates identified 23 separate PCR types, 19 with these markers later used to identify species and subspecies of T. rubrum.…”

Section: Non-transcribed Spacer Regions Of Rdnamentioning

confidence: 99%

Molecular markers useful for epidemiology of dermatophytoses

Mochizuki

Takeda

Anzawa

2015

The Journal of Dermatology

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Dermatophytosis is a very common skin disorder and the most prevalent infectious disease treated by dermatologists. Recent developments in molecular techniques have markedly changed methods of identifying dermatophytes, with these methods showing intraspecies polymorphisms in some molecular markers. Intraspecies subtyping and strain differentiation have made possible the tracking of infections, the identification of common sources of infections and recurrence or reinfection after treatment. This review describes methods of intraspecies differentiation using mitochondrial DNA, random amplification of polymorphic DNA, non-transcribed spacer regions of ribosomal RNA genes and microsatellite markers, as well as their usefulness and limitations.

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“…Trichophyton rubrum is the most prevalent dermatophyte, accounting for about 80% of dermatomycoses that affect keratinized tissues such as skin, hair, and nails [ 1 ]. Moreover, these infections play an important role in the scenario of opportunistic infections in immunocompromised patients [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Response ofTrichophyton rubrumduring Coculture on Keratinocytes Exposed to Antifungal Agents

Komoto

Bitencourt

Silva

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid α-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 µM to α-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets.

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Trichophyton rubrumDNA strain switching increases in patients with onychomycosis failing antifungal treatments

Cited by 21 publications

References 30 publications

High prevalence of mixed infections in global onychomycosis

High prevalence of mixed infections in global onychomycosis

Molecular markers useful for epidemiology of dermatophytoses

Gene Expression Response ofTrichophyton rubrumduring Coculture on Keratinocytes Exposed to Antifungal Agents

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