Int.J.Curr.Microbiol.App.Sci (2019) 8(11): 1877-1886 International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 8 Number 11 (2019) Journal homepage: http://www.ijcmas.com Review Article https://doi.org/10.20546/ijcmas.2019.811.220 Pathogenesis and Clinical Significance of Dermatophytes Shyama Datt* and Thakur Datt Department of Microbiology, UCMS & GTB Hospital, Dilshad Garden, Delhi-95, India *Corresponding author ABSTRACT Despite the superficial localization of most dermatophytosis, host-fungus relationship in these infections is complex and still poorly elucidated. K e yw or ds Though many efforts have been accomplished to characterize secreted Dermatophytes, dermatophytic proteases at the molecular level, only punctual insights have Pathogenesis, been afforded into other aspects of the pathogenesis of dermatophytosis, Trichophyton, Microsporum , such as fungal adhesion, regulation of gene expression during the infection Ergosterol process, and immunomodulation by fungal factors. However, new genetic Article Info tools were recently developed, allowing a more rapid and high-throughput functional investigation of dermatophyte genes and the identification of Accepted: 17 October 2019 new putative virulence factors. In addition, sophisticated in vitro infection Available Online: models are now used and will open the way to a more comprehensive view 10 November 2019 of the interactions between these fungi and host epidermal cells, especially keratinocytes. Introduction Epidermophyton (1,2). Due to their high affinity for the keratinized tissues, Dermatophytes dermatophytes are responsible for most of superficial mycosis affecting human skin or Infections pertaining to mankind particularly nails. those affecting the keratinized tissues are of serious concerns worldwide and are increasing Classification on a global scale. Dermatomycoses are infections of the skin, hair and nail caused as a Dermatophytes are fungi that invade and result of colonization of the keratinized layers multiply within keratinized tissues (skin, hair, of the body. This colonization is brought about and nails) causing infection (1). Based upon by the organisms belonging to the three genera their genera, Dermatophytes can be classified namely Trichophyton, Microsporum and into three groups: Trichophyton (which causes 1877 Int.J.Curr.Microbiol.App.Sci (2019) 8(11): 1877-1886 infections on skin, hair, and nails), geographical distribution. The predominant Epidermophyton (which causes infections on cause of Dermatophytic infections is skin and nails), and Microsporum (which Trichophyton followed by Epidermophyton causes infections on skin and hair). Based and Microsporum. Within the genus upon the mode of transmission, these are been Trichophyton, Trichophyton rubrum is the classified as anthropophillic, zoophilic, and predominant etiological agent accounting for geophilic. Finally, based upon the affected 69.5% followed by Trichophyton site, these are been classified clinically into mentagrophytes, Trichophyton verrucosum tinea capitis (head), tinea faciei (face), tinea and Trichophyton tonsurans (5-7). barbae (beard), tinea corporis (body), tinea manus (hand), tinea cruris (groin), tinea pedis According to the World Health Organization (foot), and tinea unguium (nail).Other clinical (WHO) survey on the incidence of variants include tinea imbricata, tinea dermatophytic infection, about 20% the people pseudoimbricata, and Majocchi granuloma(3). worldwide present with cutaneous infections (8). Trichophyton Pathogenesis and clinical presentation The genus Trichophyton includes 24 species. The colonies on agar media are powdery, The possible route of entry for the velvety or waxy. The predominant spore type Dermatophytes into the host body is injured is micro conidia with sparse macro conidia skin, scars and burns. Infections caused by (4). arthrospores or conidia. Resting hairs lack the essential nutrient required for the growth of Microsporum the organism. Hence, these hairs not invaded during the process of infection (22). The genus Microsporum includes 16 species. The colony morphology of Microsporum The pathogen invades the uppermost, non- species on agar surface is either velvety or living, keratinized layer of the skin namely the powdery with white to brown pigmentation stratum corneum, produces exo-enzyme (4). keratinase and induces inflammatory reaction at the site of infection (23-26). The customary Epidermophyton signs of inflammatory reactions such as redness (ruber), swelling (induration), are seen The genus Epidermophyton includes only 2 at the infection site. Inflammation causes the species. The colonies are slow-growing, pathogen to move away from the site of powdery and unique brownish yellow in infection and take residence at a new site. This colour. This genus is devoid of micro conidia. movement of the organism away from the Macro conidia are abundant and produced in infection site produces the classical ringed clusters (4). lesion (27) (Fig. 1–4). Distribution frequency of dermatophytes Figure 3: The schematic route of entry of and dermatophytosis dermatophytes into the host system and onset the host when pathogen entry. All the three genera of Dermatophytes namely Trichophyton, Microsporum and The infections caused by Dermatophytes Epidermophyton are worldwide in commonly referred to as “tinea” or “ring- 1878 Int.J.Curr.Microbiol.App.Sci (2019) 8(11): 1877-1886 worm” infections due to the characteristic spores begins by 4 h. In a nail plate model, ringed lesions (9). Based on the site of adherence and germination of T. infection, the tinea infections are referred to as mentagrophytes arthrospores were observed at tinea capitis (scalp), tinea corporis or tinea 6 h and side branches at 16 h (17). The early circinata (non-hairy, glaborous region of the stages of T. mentagrophytes infection were body), tinea pedis (“Athletes‟ foot”; foot), investigated using skin explants of full tinea ungium (“Onychomycosis”; nail), tinea epidermis thickness (18). Adherence was mannum (hands) (Figure 3), tinea barbae maximum at 12 h, germination had started by (“Barbers‟ itch”; bearded region of face and 24 h, and penetration of the stratum corneum neck), tinea incognito (steroid modified), tinea occurred after 3 days. imbricata (modified form of tinea corporis), tinea gladiatorial (common among wrestlers‟) Little is known about the factors that mediate and tinea cruris(“Jocks‟ itch”; groin) (10). adherence of dermatophytes. The ability of T. rubrum to adhere to epithelial cells has been Dermatophytes can survive solely on outer attributed to carbohydrate-specific adhesins, cornified layers of the skin.(11,12) The ability expressed on the surface of microconidia (19). of certain fungi to adhere to particular host From a morphological point of view, fibrillar arises from numerous mechanisms and host projections have been observed in T. factors, including the ability to adapt to the mentagrophytes during the adherence phase human body.(11) Natural infection is acquired (20, 21). At the skin surface, long and sparse by the deposition of viable arthrospores or fibrils connect fungal arthroconidia to hyphae on the surface of the susceptible keratinocytes and to each other, while in the individual.(13) After the inoculation in the inner skin layers, newly formed arthroconidia host skin, suitable conditions favor the show thin and short appendices covering their infection to progress through the following entire surface; the latter beg into vanish as a stages.(14) large contact area is established between conidia and skin tissue (21). Based on the Adherence findings made in the yeast Candida albicans, where secreted aspartic proteases (Saps) have The kinetics of adherence to the skin or nail been shown to play a fundamental role in surface was investigated in several fungal adherence to epithelia (22-23), so that Trichophyton and Microsporum species, using is dermatophytic-secreted proteases could different experimental models and microscopy facilitate or even be necessary for efficient techniques. These studies showed a time- adherence. We have checked the expression dependent increase in the number of adhering pattern of Exoprotease and Endoprotease spores, followed by germination and invasion genes with their non-protease genes in real of the stratum corneum by hyphae growing in time PCR from that data we hypothesised that multiple directions. Zurita and Hay (14) the Endoprotease have majorly expressed in observed that maximum adherence of dermatophytic patient during infection. Trichophyton spp. arthroconidia to keratinocytes in suspension occurred within Penetration 3–4 h. Aljabre et al., (15, 16) used stripped sheets of stratum corneum or separate Dermatophytes are provided with an arsenal of keratinocytes to demonstrate that adherence of proteases aimed at the digestion of the keratin Trichophyton mentagrophytes arthroconidia is network into assimilable oligopeptides or maximum by 6 h and that germination of these amino acids. (24) Once established, the spores 1879 Int.J.Curr.Microbiol.App.Sci (2019) 8(11): 1877-1886 must germinate and penetrate the stratum pathophysiological status of the host. In corneum at a rate faster than desquamation. general, the zoophilic species cause more Penetration is accompanied by dermatophytes inflammatory infections, which may heal secreting multiple serine-subtilisins and spontaneously and result in relative resistance metallo-endoproteases (fungalysins) formerly to re-infection. The anthropophilic