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Dermatophytes and Dermatophytoses
Dermatophytes and Dermatophytoses
DOI 10.1007/s11046-017-0114-z
EDITORIAL
Fungal pathogens predominant on the hair, skin, and [1]. The present special issue builds upon the previous
nail (dermatophytes) cause most common mycotic coverage after a gap of 8 years. Twenty-one invited
diseases (dermatophytoses) worldwide. Although articles contributed by 60 experts all over the word
fatal rarely, dermatophytoses manifest as significant focus on four major themes including pathogenhost
causes of hair and nail loss, inflammation, pustules, genetics, clinical prevalence, presentation, therapy and
itching, and scaling. Mycopathologia continues to laboratory diagnosis, and hostpathogen interactions.
maintain a dual focus on both dermatophytes and de Hoog, Graser, and colleagues describe a taxo-
dermatophytoses. The balanced coverage of the clinical nomic reappraisal of dermatophytes in the first article
and laboratory developments had been reinvigorated by of this special issue [2]. Notably, 13 new combinations
periodic special issues. A 2008 special issue covered 14 are proposed based on the internal transcribed spacer
relevant topics that generated over 1600 citations so far (ITS) regions 1 and 2 of ribosomal DNA (rDNA) and
partial LSU, the ribosomal 60S protein, and fragments
of b-tubulin and translation elongation factor 3. The
J. P. Bouchara affected taxa are the geophilic and zoophilic Mi-
UNIV Bretagne-Loire, University of Angers, University crosporum species. Seven phylogenetic clades were
of Brest, Host-Pathogen Interactions Study Group (EA
identified and the nomenclature summarized. All
3142), Angers, France
e-mail: [email protected] anthropophilic Trichophyton, as well as Epidermophy-
ton, are within the derived clades. This most compre-
J. P. Bouchara hensive overview of the family Arthrodermataceae is
Laboratory of Parasitology-Mycology, Angers University
likely to become the sole source for authentic infor-
Hospital, Angers, France
mation of pathogenic dermatophytes. This seminal
B. Mignon work is also likely to guide future taxonomic and
Department of Infectious and Parasitic Diseases, Faculty phylogenetic studies [2]. Genetic manipulations of
of Veterinary Medicine, Fundamental and Applied
pathogenic fungi are essential tools to get a deeper
Research for Animal Health (FARAH), University of
Liege, Liege, Belgium insight into pathogenic mechanisms, and finding a
e-mail: [email protected] better cure eventually. These experimental approaches
took a while to become available for the dermatophytes
V. Chaturvedi (&)
as they exhibit high frequency of non-homologous
California Institute for Medical Research, San Jose, CA,
USA recombination. Alshahni and Yamada map the recent
e-mail: [email protected] progress in the transformation and manipulations of
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2 Mycopathologia (2017) 182:14
gene expressions among various dermatophyte species Their analysis stretching back to the beginning of the
[3]. An inventory of dominant selectable markers, an twentieth century focuses on the socioeconomic
inducible promoter, and marker recycling system is conditions, life style changes, and the introductions
provided to highlight both the challenge and progress of new drugs as the major drivers of these changes.
being made with the molecular toolbox. The authors Hays rich clinical and research experience with Tinea
include a brief description of the whole genome capitis provides an excellent coverage of the topic with
sequences and transcriptomes of dermatophytes and initial comments on great advances made in the
their potential to enhance the selection and experi- understanding of hostpathogen interactions [8]. His
mental targeting of genes and genomes of dermato- expert review covers epidemiology, clinical varieties,
phytes [3]. Metin and Heitman describe the extant conditions, differential diagnosis, management, and
evidence for sexual reproduction in the dermatophytes community control. Also highlighted is the introduc-
[4]. A detailed insight into the organization of the two tion of more sensitive molecular diagnostic tests in
mating loci in different phylogenetic clade is pre- routine clinical practice. In concluding comments,
sented. The authors also include comparative schemat- Prof. Hay highlights the recent discovery of CARD9
ics on the organization of the MAT locus in different deficiency as a risk factor and the opportunity for the
pathogenic fungi. The concluding comments address future development of a vaccine [8]. Asz-Sigall and
the observed sexual reproduction in geophilic and colleagues provide an overview of dermatophyte nail
zoophilic species and its absence in anthropophilic infections termed onychomycosis or Tinea unguium
species [4]. It has been known for almost thirty years [9]. This clinical condition has assumed great signif-
that there is a significant genetic and physiological icance given increased incidences of T. rubrum
variation among the clinical isolates of dermatophytes. infections of the nails and the therapeutic challenges.
Mochizuki, Takeda and Anzawa detail the tools for the The epidemiology, etiology, clinical features, diagno-
molecular epidemiology of dermatophytes so as to sis, various treatment options, and the criteria for cure
highlight the inter- and intraspecies differentiations are covered with most appropriate literature citations
among various pathogens [5]. Their overview details [9]. The appearance of the typical dermatophyte lesion
some investigations on the application of mitochon- on the skin might be mimicked by other, non-fungal
drial DNA analysis, random amplification of polymor- etiologies. Libon and colleagues highlight the clinical
phic DNA (RAPD), sequencing of the ITS or non- and histopathological appearances of dermatophyte
transcribed spacer (NTS) regions of rDNA, and infections of hair and skin with a special focus on the
microsatellite analysis for genotyping. Some host- intertriginous regions [10]. The lucid description is
and pathogen-specific attributes of dermatophytes enhanced with many illustrative photographs from the
have already been discovered. Nevertheless, the more affected patients. Equally importantly, these experts
refined discriminatory power of the whole genome go on to cover the differential diagnostic features and
comparisons will likely lead to more discoveries of the methods for the relevant skin lesions [10]. Pin presents
strain variations [5]. All human populations are a comprehensive overview of the clinical presenta-
exposed to dermatophytes, but dermatophytoses are tions of dermatophytoses in animals [11]. Several
more prevalent in certain communities and ethnic illustrative photographs accompany the expert com-
groups. Does host genetics plays a role in susceptibility mentary. Additionally, the clinical presentations of
to dermatophytes? This intriguing question is the non-dermatophytic dermatoses mimicking dermato-
central theme of the article by Abdel-Rahman [6]. The phytoses are also compared and contrasted. Guptas
theme is summarized in schematic that goes to unique perspective on the antifungal drugs against
highlight the genetic evidence of association and dermatophytes includes a progress report since the
causal relationships. Some genetic loci and their publication of a similar article in an earlier special
putative roles are summarized succinctly. The author issue of Mycopathologia [12, 13]. In collaborations
concludes by highlighting the need for future genetic with colleagues, Dr. Gupta describes the main treat-
studies so as to define the host genes critical in ment modalities in use against various forms of
susceptibility and resistance to dermatophytoses [6]. Tinea. Although focused on studies from Europe
Zhan and Liu cover the rise and fall of various and North America, the pros and cons of various drugs
dermatophytes as prominent pathogens globally [7]. and dosages are covered in sufficient detail with
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Mycopathologia (2017) 182:14 3
citations of relevant publications. The authors also diagnostic tools for dermatophytoses of hair, skin, and
provide insight as to how new formulations of existing nail [17]. The advantages are manyhigher sensitiv-
drugs as well as drug delivery innovations are ity and specificity, more accuracy, and ability to find
invigorating the treatment options despite a lack of fungal elements independently of prior treatment
new classes of antifungal drugs against dermatophytes history. A few challenges remain including the
[13]. As the pharmaceutical choices for dermatophy- feasibility, affordability, and a lack uniformity among
toses are perceived to be limited, the natural products the preparative methods used for DNA extraction. The
are being still evaluated for their direct efficacy and as authors present comprehensive literature overview
the source for new drugs. Lopes and colleagues review and alternate scenarios for the selection of traditional
published evidence of anti-dermatophytic properties and molecular methods [17]. Hayette and Sacheli
in various classes of plant-derived compounds and deviate from the obvious to provide an excellent
their active chemical constituents [14]. They highlight overview of new pathogenic species of Microsporum
the need for more standardization of test methods and and Trichophyton [18]. Next, they summarize recent
ex vivoin vivo testing. clinical reports on rare pathogens of this group. Lastly,
Dermatophytes are not only the most common they highlight the unusual clinical manifestations of
fungal infections, but they are most likely to be the common pathogens included among dermato-
diagnosed both by the physicians and by the labora- phytes. These details are interspersed with relevant
torians by direct microscopy. Pihet and Le Govic focus references to any documented transfers of the etiologic
on the reappraisal of the direct examination and agents from animals or soil to humans [18].
culture for dermatophyte diagnostics [15]. The authors Dermatophytes must reprogram their cellular pro-
cover the techniques in details, evaluate merits and cesses to sense and adapt to the host surfaces. Martinez-
shortcomings as well as recent improvements, and end Rossi and colleagues highlight the fungal transcription
with the focus on the demonstrated sensitivity of factors, proteins, and enzymes involved in this multi-
molecular methods. The availability of commercial factorial process [19]. The adaptations are made in the
DNA kits is likely to promote wider acceptance of face of specific host factors elucidated in response to the
non-culture-based tests although the culture remains infection. The challenges posed by unique pH of the
relevant to confirm atypical pathogens [15]. LOllivier host surfaces and the optimal expression of fungal
and Ranque share extensive experiences with keratinases at such a pH are covered in great detail. The
MALDITOF dermatophyte identifications [16]. authors make frequent reference to the available whole
Many helpful tips for the sample preparations, anal- genome sequences of many dermatophytes, which also
ysis, and reference spectra library vividly illustrate provides a roadmap for future investigations aimed at
their rich expertise. The promise of this approach is understanding the pathogenesis of dermatophytes [19].
weighed against the evidence from ten published Cambier and colleagues start their overview of pub-
studies that report 13.5100% accuracy in the identi- lished animal models by providing a context for the
fication of dermatophytes. The authors emphasize the continuing need for the experimental studies [20]. Next,
need to expand the commercial reference spectra they do a critical review of published mouse, guinea
libraries of uncommon and rare species so as to make pig, and rat models. The overview is organized into
MALDITOF as the gold standard for identification of separates studies on pathogenesis, host response, or
dermatophytes [16]. As stated earlier, the diagnosis of efficacy of antifungal treatments. The authors conclude
dermatophytoses is unique among fungal infections as by providing a critique of approaches adopted so far and
it could be performed both by the laboratory and by the a possible solution to establishing a workable model in
physician often right at the time of the patient visit. In nude mice [20]. Yoshikawa and colleagues detail T.
the USA, the federal laboratory regulations exempt rubrum interactions with mouse J774 macrophage-like
this process from rigorous oversight by treating it as a cells [21]. The authors found T. rubrum-induced cell
unique provider performed microscopy (PPM). death and release of IL-1b. They also profiled pro-
Some new developments indicate that direct micro- teomic changes in the macrophages following fungal
scopy might not be the best diagnostic approach for the interactions. The specific observations in this
dermatophytoses. Verrier and Monod present a strong tractable cell line strongly indicate its relevance as an
case for the primacy of PCR and real-time PCR as ex vivo model [21]. Heinen and colleagues focus on the
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4 Mycopathologia (2017) 182:14
emerging role of Th17 pathway in immunity against 5. Mochizuki T, Takeda K, Anzawa K. Molecular markers
dermatophytoses [22]. The available direct evidence useful for intraspecies subtyping and strain differentiation
of dermatophytes. Mycopathologia. 2016:19. doi:10.1007/
from animal studies and indirect evidence from recep- s11046-016-0041-4.
tors and APCs are summarized in informative schemat- 6. Abdel-Rahman SM. Genetic predictors of susceptibility to
ics. The exciting possibility of finding an innate dermatophytoses. Mycopathologia. 2016:110. doi:10.
mechanism for Th17 pathway involvement in dermato- 1007/s11046-016-0046-z.
7. Zhan P, Liu W. The changing face of dermatophytic
phytoses is emphasized [22]. Yoshikawa and De infections worldwide. Mycopathologia. 2016:110. doi:10.
Almeida revisit the role of innate immunity against 1007/s11046-016-0082-8.
dermatophytosis by focusing on the phagocytic cells 8. Hay RJ. Tinea capitis: current status. Mycopathologia.
including neutrophil extracellular traps (NETs) [23]. 2016:17. doi:10.1007/s11046-016-0058-8.
9. Asz-Sigall D, Tosti A, Arenas R. Tinea unguium: diagnosis
The authors cover recent studies on the host pattern and treatment in practice. Mycopathologia. 2016:16.
recognition receptors (PRRs) and pathogen-associated doi:10.1007/s11046-016-0078-4.
molecular patterns (PAMPs) involved against dermato- 10. Libon F, Nikkels-Tassoudji N, Dezfoulian B, Arrese JE,
phytes. Also covered is the role of inherited CARD9 Nikkels AF. Non-dermatophyte dermatoses mimicking
dermatophytoses in humans. Mycopathologia. 2016:111.
deficiency as a risk factor for dermatophytoses. doi:10.1007/s11046-016-0059-7.
Although still in its infancy, insights into how der- 11. Pin D. Non-dermatophyte dermatoses mimicking dermato-
matophytes avoid neutrophils, and the induction of phytoses in animals. Mycopathologia. 2016:114. doi:10.
NETs would further promote our understanding of 1007/s11046-016-0090-8.
12. Gupta A, Cooper E. Update in antifungal therapy of der-
innate immune responses against this group of fungal matophytosis. Mycopathologia. 2008;166(5):353367.
pathogens [23]. doi:10.1007/s11046-008-9109-0.
We are confident that this sweeping overview of the 13. Gupta AK, Foley KA, Versteeg SG. New antifungal agents
dermatophytes and dermatophytoses served to con- and new formulations against dermatophytes. Myco-
pathologia. 2016:115. doi:10.1007/s11046-016-0045-0.
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progress made during the last decade. However, as native to conventional therapy for dermatophytosis?
always, more scientific progress leads to additional Mycopathologia. 2016:125. doi:10.1007/s11046-016-
unanswered questions. We would welcome insight 0081-9.
15. Pihet M, Le Govic Y. Reappraisal of conventional diagnosis
into how many species of dermatophytes there really for dermatophytes. Mycopathologia. 2016:112. doi:10.
are, how dermatophytes evolved as pathogens, how do 1007/s11046-016-0071-y.
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pathogenic potential, where to find untapped chemical identification. Mycopathologia. 2016:110. doi:10.1007/
s11046-016-0080-x.
moieties to develop new drugs, and finally, is culture- 17. Verrier J, Monod M. Diagnosis of dermatophytosis using
independent diagnostic testing likely to replace direct molecular biology. Mycopathologia. 2016:110. doi:10.
microscopy and culture? It is our earnest hope to cover 1007/s11046-016-0038-z.
these and other interesting developments in the next 18. Hayette M-P, Sacheli R. Unusual species of dermatophytes:
rarely identified or new? Mycopathologia. 2016:111.
special issue in 2028! doi:10.1007/s11046-016-0066-8.
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