DOI: 10.1128/spectrum.01087-26 ISSN: 2165-0497
Dermatophytosis beyond
Trichophyton indotineae
: genomic characterization of rare keratinophilic fungi
Myriodontium keratinophilum
and
<
Amtoj Kaur, Sandhyarani Mahanto, Gulnaz Bashir, Meenakshi Malik, Bashir Ahmad Fomda, Farah Sameem, Arijit Pal, Syed Khurshid Ahmad, Hardeep Kaur, Perumal Vivekanandan, Anuradha Chowdhary ABSTRACT
Fungal skin infections represent the fourth most prevalent disease globally, predominantly attributed to dermatophyte species such as
Trichophyton
. Nevertheless, sporadic instances of dermatophytosis may also arise from opportunistic, uncommon fungi. This study documents the association of keratinophilic fungi,
Myriodontium keratinophilum
and
Aphanoascus verrucosus
, with cases of dermatophytosis in Kashmir, North India. Internal transcribed spacer region sequencing of 64 isolates obtained from skin, hair, and nail samples of 62 patients identified 61% of isolates (
n
= 39) as
M. keratinophilum
, followed by
Trichophyton indotineae
and
A. verrucosus
in 20% (
n
= 13) and 19% (
n
= 12) cases, respectively. Furthermore, the first hybrid
de novo
genome assembly of
M. keratinophilum
is reported in the present study. Genomic analysis of both
M. keratinophilum
and
A. verrucosus
species revealed median intra-species single nucleotide polymorphism (SNP) differences of 100 and 27, respectively, suggesting highly related strains in the patient population.
De novo
functional annotation identified a higher number of coding regions in
M. keratinophilum
compared to
T. indotineae
and
A. verrucosus
, including carbohydrate-active enzymes (CAZymes) exhibiting unique substrate affinities and subtilisin 3 (
SUB3
) gene, previously implicated as a potential virulence gene in dermatophytes. Notably, in addition to all the multidrug transporters encoded by
Trichophyton
species,
M. keratinophilum
genome contains six putative ATP-binding cassette (ABC) transporters showing 40%–70% sequence similarity with the
CDR1
gene.
M. keratinophilum
exhibited reduced susceptibility to multiple antifungals, including high minimum inhibitory concentrations (MICs) (>16 mg/L) against griseofulvin and itraconazole. Importantly, itraconazole is a primary therapeutic agent for terbinafine-resistant
T. indotineae
infections, underscoring the necessity for early and accurate identification and intervention of dermatophytic infections.
IMPORTANCE
The study reports cases of dermatophytosis associated with two rare keratinophilic fungi, i.e.,
Myriodontium keratinophilum
and
Aphanoascus verrucosus
. The cases mainly presented as tinea corporis and cruris, commonly caused by
Trichophyton indotineae
in the Indian subcontinent, which may remain undiagnosed due to a lack of molecular identification. Furthermore, the first-ever genome report of
M. keratinophilum
and its
ab initio
functional annotation is useful for further studies and management of opportunistic pathogens that exhibit reduced susceptibility towards itraconazole, the first-line drug of treatment for terbinafine-resistant
T. indotineae
infections. An early correct molecular identification of the etiologic agents of skin infections is warranted to tackle the new agents of dermatophytosis at the earliest stage.