Virulence Factors and Pathogenesis
The dermatophytes are transmitted by direct contact with an infected host or by contact with contaminated objects and environment. The successful initiation of infection is closely related to the capability of the pathogenic fungus to overcome the host resistance mechanisms.
The adherence to the keratinized tissue, germination of the arthroconidium, and stratum corneum penetration are the first steps in this process (Hube et al. 2015; Chinnapun 2015). Mechanical disruption of the stratum corneum consequent to microtrauma of different origin (e.g., due to ectoparasites in cats and dogs) appears to be important aspect in facilitating penetration and invasion of hair follicles (Miller et al. 2013). Three crucial steps to overcome cutaneous barriers and cause infection, i.e., adhesion, germination, and invasion of the stratum corneum, are separated by variously long time periods that range from several hours to several days depending on particular species (Aljabre et al. 1993; Rashid et al. 1995; Duek et al. 2004). It has been suggested that pathogenic dermatophytes express carbohydrate-specific adhesins on conidia surface that recognize mannose and galactose on the skin surface during adhesion (Esquenazi et al. 2004). Additionally, secreted proteases are required for the adherence process and participate in invasion of epidermis (Baldo et al. 2008; Baldo et al. 2010; Shi et al. 2016). Keratin is a hard and compact protein, which is unavailable as a nutrient source to the majority of organism in the nature. Its degradation and utilization during penetration and infection are considered a major virulence attribute. The dermatophytes dispose expanded sets of endopeptidases, exopeptidases, and secreted proteases reserved for that purposes (Burmester et al. 2011; Martinez-Rossi et al. 2017). In addition, the process of keratinolysis is facilitated by sulfite efflux, a reducing agent which can cleave keratin-stabilizing cystine bonds and whose production from cystine depends on the cysteine dioxygenase (Grumbt et al. 2013).Other tentative virulence factors comprise production of siderophores to overcome iron deficiency (Mor et al. 1992; Krober et al. 2016), melanin with immunomodulatory properties (Youngchim et al. 2011), expression of homologues of multidrug resistance class of ABC transporters modulating susceptibility to antifungals (Fachin et al. 2006; Ghannoum 2016), or production of toxic exometabolites. Genome sequences of dermatophytes revealed a high number of secondary metabolite gene clusters, some of them are upregulated during keratinocyte infection (Burmester et al. 2011; Martinez et al. 2012; Yin et al. 2013). Toxin Xanthomegnin was predicted as a virulence factor and can be extracted from infected keratinized tissues but is not detected in uninfected tissues (Gupta et al. 2000; Kandemir et al. 2015).
In general, the stepwise process of host infection is similar across the species; however, the ability to elicit a host reaction upon infection is species-specific. Different dermatophytes induce different immune responses in the host in terms of quality and intensity. They may induce a high level of tissue damage and inflammatory reaction, but in particular host species or individuals, they can manipulate the host' s immune response, ensuring survival and prolonging chronic infection (Hube et al. 2015). The interaction of host cells (keratinocytes and immune cells) and dermatophyte and recognition of fungal antigens and secreted enzymes by host are basis for immune response. Cell-mediated immunity and production of various cytokines are widely considered to be involved in modulating the immune response (Achterman and White 2011; Hube et al. 2015; Chinnapun 2015; Martinez-Rossi et al. 2017).
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