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Citation Information : Postępy Mikrobiologii - Advancements of Microbiology. Volume 58, Issue 2, Pages 165-176, DOI: https://doi.org/10.21307/PM-2019.58.2.165
License : (CC-BY-NC-ND 4.0)
Published Online: 15-October-2019
Dermatophytoses are skin diseases related to the infection of surface layers of skin and other keratinised structures such as hair and nails, caused by fungi referred to as dermatophytes. The scientific literature provides descriptions of over 50 dermatophytic species classified in the
1. Introduction. 2. Dermatophytoses in dogs and cats. 2.1. Diagnostic problems in zoophilic dermatophytoses. 2.2. The prevalence of dermatophytosis in dogs and cats. 2.3. Factors predisposing to dermatophytosis. 2.4. Breed predilections in dermatophyte infections. 3. Pathogenesis and dermatophyte virulence factors. 3.1. Development of dermatophyte infection. 3.2. The pathogenesis of infection. 3.3. Dermatophyte virulence factors. 3.4. Clinical symptoms in canine and feline dermatomycoses. 3.5. Host immune response. 4. SummaryTranslated
1. Wprowadzenie. 2. Dermatofitozy u psów i kotów. 2.1. Problemy diagnostyczne w dermatofitozach zoofilnych. 2.2. Prewalencja dermatofitoz u psów i kotów. 2.3. Czynniki predysponujące do dermatofitoz. 2.4. Predylekcje rasowe w infekcjach dermatofitowych. 3. Patogeneza i czynniki wirulencji dermatofitów. 3.1. Rozwój infekcji dermatofitowej. 3.2. Patogeneza infekcji. 3.3. Czynniki wirulencji dermatofitów. 3.4. Objawy kliniczne w dermatomykozach psów i kotów. 3.5. Odpowiedź immunologiczna gospodarza. 4. Podsumowanie
Dermatomycoses are skin diseases caused by an infection of its surface layers and other keratinized structures such as hair and nails by fungi referred to as dermatophytes . Based on their adaptation to life, these eukaryotic microorganisms may be divided into three groups: those that attack people, referred to as anthropophilic, those associated with animals – zoophilic and those that live in the soil – geophilic ones [35, 44]. Dermatophytes belong to eurybiotic organisms, present around the world . Surface skin mycoses constitute an important disease entity due to their highly contagious nature, significant zoonotic potential and poorly outlined clinical symptoms which may additionally imitate other diseases. Dermatomycoses are self-limiting in most immunocompetent hosts and may become eradicated on their own within a few weeks or months. Nevertheless, a proper diagnosis and the introduction of appropriate treatment not only shortens the time needed to cure a patient, but also prevents the arthrospores of dermatophytes from spreading onto other animals and people that remain in direct contact with an infected specimen or use the same products for care and the maintenance of hygiene [40, 43].
The scientific literature provides descriptions of over 50 dermatophytic species classified in the following genera: Trichophyton (Malmsten 1848), Microsporum (Fat 1843), Epidermophyton (Sabour. 1907), Nannizzia (Stockdale 1961), Arthroderma (Curr. 1860), Lophophyton (Matr. & Dassonv. 1899) and Paraphyton (Y. Gräser, Dukik & de Hoog 2018) [28, 48]. Zoophilic species, with over 30 representatives enumerated by mycologists at present, constitute a numerous group of dermatophytes [28, 48]. Zoophilic dermatophytes have created a number of adaptations, especially with regard to their metabolic activity, which enable their survival in the stratum corneum of animal hosts . The most frequently enumerated species of zoophilic dermatophytes of large epidemiological significance include Trichophyton mentagrophytes (C.P. Robin 1895), associated with infections in fur animals, Trichophyton verrucosum (E. Bodin 1902), which is characterized by a particular affinity for bovine keratin, Microsporum canis (E. Bodin ex Guég. 1902), associated with infections in dogs and cats, Microsporum equinum (E. Bodin ex Guég. 1907) as well as Trichophyton equinum (Gedoelst 1902) which attacks horses, Microsporum persicolor (Guiart & Grigoraki 1928), isolated from rodents, Microsporum nanum (C.A. Fuentes 1956) isolated from swine [40, 41, 43, 106, 109].
Clinical practitioners and microbiological diagnosticians most often use the nomenclature of asexual forms of dermatophytes, referred to as anamorphs. In reality, it is precisely these forms that are most often isolated from clinical cases of dermatomycoses in animals (the Trichophyton and Microsporum genera) [44, 106]. It should be remembered, however, that in laboratory conditions the sexual stages of some species of dermatophytes, referred to as perfect stages or teleomorphs, were identified which, in turn, led to distinguishing the Arthroderma genus and, indirectly, also to the formation of complexes of species: the Trichophyton benhamiae complex, the Trichophyton mentagrophytes complex and the Microsporum canis complex [28, 100, 101]. The main problem encountered by diagnosticians, resulting from the conducted experiments in sexual crossing, is the presence of a dual system for the classification and naming of dermatophytes. The traditionally used name T. mentagrophytes is, strictly speaking, a complex of several different species of both zoophilic and anthropophilic dermatophytes, which have been distinguished from one another on the basis of preferences for the type of keratin, morphological, molecular features and sexual stages [74, 100, 101]. Zoophilic species belonging to the anamorphic T. mentagrophytes complex have been teleomorphically classified as Arthroderma benhamiae (Ajello & S.L. Cheng 1967) based on experiments consisting of conjugating strains isolated from rodents – including guinea pigs, as well as from dogs and cats. Meanwhile, the Arthroderma vanbreuseghemii teleomorph (Takashio 1973) corresponds to zoophilic strains of T. mentagrophytes, isolated mainly from mice and chinchillas, but in many cases also from dogs and cats, as well as, most importantly, from people who remain in contact with pets that demonstrate clinical symptoms and those that are asymptomatic carriers [33, 96]. In turn, Trichophyton interdigitale (Priestley 1917) is a strictly anthropophilic, anamorphic species belonging to the T. mentagrophytes complex, for which the formation of the perfect form has not been demonstrated . It ought to be remembered that the Amsterdam Declaration on fungal nomenclature adopted in 2011 indicated that each eukaryotic microorganism should only have one formally used nomenclature name .
Sexual processes are even more complicated for geophilic species, e.g. the Microsporum gypseum (Guiart & Grigoraki 1928) anamorph is now considered a complex of three separate teleomorphic species: Arthroderma fulvum (Weitzman, McGinnis, A.A. Padhye & Ajello 1986), A. gypseum (Weitzman, McGinnis, A.A. Padhye & Ajello 1986) and A. incurvatum (Weitzman, McGinnis, A.A. Padhye & Ajello 1986), in which interspecific conjugation does not occur [100, 101]. Although geophilic species of dermatophytes are most often associated with the decomposition of zoonotic keratin present in the soil, some of these organisms may cause infections in humans and animals . The natural habitat of geophilic dermatophytes are positions located around dwelling spots (burrows, dens) of specific species of land mammals . Hunting dogs that remain in contact with soil are a group that is particularly vulnerable to geophilic infections. In addition, this group of fungi may be transferred mechanically by animals on their outer shells [15, 35, 43] imitating the state of being an asymptomatic carrier, which makes it so that the difference in the ecological niches occupied by geophilic and zoophilic dermatophytes is not always clear. The diagnosis is of these dermatophytes is made significantly difficult, especially in terms of distinguishing them from infections of a zoophilic aetiology.
The discussed diagnostic problems are not the only ones encountered in the identification of zoophilic fungi. The new classification system for dermatophytes proposed by Sybren De Hoog’s team  is based mainly on the molecular criterion. Taxonomic relations within the Arthrodermataceae family are presented using a model of a phylogenetic tree constructed on the basis of analysing the ITS (Internal Transcribed Spacer) rDNA region [28, 44]. However, the determined criterion’s discriminatory ability is not strong enough to differaentiate between dermatophyte species with varying ecological adaptations . Two species: T. mentagrophytes and T. interdigitale, which, in terms of their ITS sequences, are genomically indiscrete , demonstrate completely different ecological adaptations. The first one is strictly anthropophilic, the second – zoophilic [43, 44, 46]. Similarly, the classification criterion based on ITS rDNA does not allow one to differentiate between the zoophilic T. equinum and the anthropophilic T. tonsurans . The problem also concerns dermatophytes from the Microsporum genus. Some zoophilic species, including M. canis and M. equinum, are phylogenetically closely related to anthropophilic species, such as M. ferrugineum (M. Ota 1921) and M. audouinii (Gruby 1843) [46, 49, 95]. The abovementioned examples are related to the fundamental problem in medical mycology, which is the peculiar ecological nature of dermatophytes and the occurrence of strict reservoirs associated with the host (Table I).
A review of the scientific literature from 29 of the world’s countries regarding the issue of the occurrence and prevalence of dermatophytosis in pets revealed significant differences in the prevalence of the infection. The two main factors that were most often mentioned as epidemiologically essential are the way the animal is kept (domestic animals, including free-roaming ones, wild, free-range, livestock or laboratory animals) and the type of infection (symptomatic or asymptomatic) [39, 41, 70, 71, 91]. Due to the wide scope of the applied methodology in the research conducted by various scientific centres, a direct comparison of the results was not possible, but clear trends in the prevalence of dermatophytosis in animals were noted. In comparison to animals who were asymptomatic carriers, dermatophytes were isolated more frequently from animals having clear signs of an infection, as well as from those that remained in groups and those, whose ability to move was unrestricted, which was especially true for cats. In regions with a warm climate, especially in Brazil, Chile, India, Italy and the southern part of the United States, the frequency of isolating dermatophytes from animals was clearly higher than in areas with a moderate or cool climate [12, 13, 15, 16].
Dermatophytes are considered to be pathogens, they are not a component of the skin’s microbiota, and their occurrence in animals and humans cannot be considered natural . The latest results of research concerning the skin’s microbiota in both healthy and allergic cats and dogs using Next Generation Sequencing (NGS) did not demonstrate that dermatophytes constituted part of the natural skin biota [70, 106]. These conclusions are confirmed by the current position of the community of microbiologists, indicating that all species of filamentous fungi isolated from the fur of healthy animals are the result of its contamination by spores present in the environment and do not constitute the proper flora of the skin, as in the case of bacteria [15, 75, 76].
In this context, interesting data are provided by the results of research on the fungal microbiota of feline and canine fur. A group of fungi diverse in terms of species was isolated from cats which did not demonstrate any clinical symptoms of dermatomycoses, one that comprised 15 genera, 13 of which were saprophytic fungi, mainly encompassing species from the following genera: Aspergillus (P. Micheli 1729), Alternaria (Nees 1816), Penicillium (Link 1809) and Cladosporium (Link 1816), and only two were dermatophytes: M. gypseum and A. vanbreuseghemii [41, 70, 71]. Interestingly, among species of dermatophytes isolated from 14 cats without symptoms of dermatomycosis, seven of which were kept in single-family houses, and seven in multifamily houses, the anthropophilic Trichophyton rubrum was found (Sabour 1911) . At the same time, none of the owners complained about the occurrence of any skin lesions, which was evidence of the fact that the owners did not contract the infection from cats or other members of the household. Meanwhile, in a different study, T. rubrum was identified in the fur of four out of 176 tested cats, and the owners were diagnosed with tinea pedis . It is interesting that all of the tested cats, belonging to 14 different breeds from seven breedings, had been kept exclusively in houses and remained in constant contact with each other within a breeding. Cases of leaving the breeding and entering into occasional contact with a cat which was kept exclusively outside were recorded for only one of the breedings . In turn, the fungi that were most often isolated from dogs not suffering from dermatomycoses were mould species from the Cladosporium and Alternaria genera. No species of dermatophytes were isolated .
An analysis of the frequency of diagnosing dermatmycoses in dogs and cats in veterinary clinics all around the world has led to the conclusion that symptomatic dermatophyte infections are rarely diagnosed. In a study conducted in 1988–2003 in the United States on a group of 1407 cats, it was found that dermatophytosis was only diagnosed in 45 (2.4%) cats, much less frequently than allergies and/or cases of atopic dermatitis (26%), bacterial skin infections (10%), demodicosis (6.1%), or flea infestations (5.2%) . An even lower prevalence of dermatomycoses was recorded in Canada, where only four out of 111 cats (3.6%) and 3 out of 419 dogs (0.71%) were diagnosed with it . In Europe, such tests were carried out in veterinary centres in the United Kingdom. Dermatophyte fungal infections were only found in two out of the 154 examined cats (1.3%) and in three out of the 559 dogs (0.53%) . Interesting data are provided by statistical surveys conducted in the United Kingdom on the basis of analysing the medical records of 91 veterinary clinics and practices over the course of 5 years (2009–2014). Dermatological problems in the 142 576 cats examined during this period constituted only 10.4% of the diagnosed diseases. It is a shame that the study did not classify dermatomycoses as separate disease entities which may, however, suggest that they occur very rarely and constitute a marginal problem . Meanwhile, in a work by Hobi et al. concerning the causes of pruritus in cats, in a group of 502 examined cats, 11 (2.1%) of them were diagnosed with dermatophytosis . It should be noted that the presented data concern only symptomatic infections in dogs and cats. From an epidemiological point of view, asymptomatic dermatophytoses, often referred to as the carrier state, are the most important.
The most frequently mentioned factors that predispose to the occurrence of symptomatic dermatomycoses include: the animal’s age, the ability to freely move around an open ground, density in the population and the climate in which they are [69, 73, 97]. It is reported that immature specimens (kittens and puppies) living in conditions of a high density of other animals, especially in countries characterized by a warm or humid climate, which additionally have the ability to leave their homes, are predisposed to dermatophyte infections [25, 41, 53, 106]. An important place in the assessment of factors predisposing towards infections is occupied by the animals’ immunological state. It is commonly known that diseases which cause immunosuppression may predispose cats and dogs to developing dermatomycoses, as well as another infectious diseases . Interesting data are provided by the works by Sierra et al. , Mancianti et al.  and Mignon et al.  concerning the assessment of whether fungal colonization in cats with a weakened immunological system, including asymptomatic carriers of dermatophytes, may constitute a factor that increases the risk of endogenous infections [69, 73, 97]. In the first of the enumerated studies, the skin’s mycobiota was tested in seropositive cats for FIV (Feline immunodeficiency virus) (n = 24), FeLV (Feline leukemia virus) (n = 10) or both these viruses, present in one specimen at the same time (n = 1) in comparison to the mycobiota of cats which, although suffering from other immunological conditions, were seronegative towards these viruses (n = 50). The study demonstrated that FIV and FeLV seropositive cats were characterized by a greater diversity of the saprophytic fungal biota of the skin, and, in particular, the fungi from the Malassezia genus (Baill. 1889). Meanwhile, in the case of dermatophytes, there was no difference between seropositive and seronegative cats, and the isolated species included M. canis, M. gypseum, M. persicolor and Trichophyton terrestre . In Mancianti’s work, the skin’s mycobiota of FIV seropositive cats (n = 35) and that of cats seronegative towards this virus (n=55) were compared . These cats originated from domestic breedings, animal shelters or were roaming the urban space freely. M. canis was isolated from 26 out of the 35 FIV seropositive (FIV+) and 14 out of the 55 FIV seronegative (FIV–) cats, in spite of the fact that the animals did not demonstrate any clinical symptoms indicating the presence of dermatomycosis. A significant shortcoming of the presented studies is the lack of dividing the animals into groups on the basis of their habitats. For this reason, it is impossible to determine whether FIV+ cats from domestic breedings, shelters or free-roaming ones are more susceptible to M. canis transmissions, or whether there is no such correlation. Contradictory data are provided by the results of studies conducted by Mignon et al., in which no relationship between an FIV infection and being a carrier of dermatophytes was found . Final conclusions have to be confirmed by more extensive analyses.
There are very few scientific reports on the comorbidity of dermatomycoses and other diseases which cause immunosuppression. One case of a cat with xanthomata on the skin along with comorbid demodicosis and dermatophytosis is available . In two studies on treating pemphigus foliaceus in cats using immunosuppressive medicines, the simultaneous development of dermatophytosis was not found [58, 90]. One cat developed dermatophytosis caused by M. canis over the course of being treated for alopecia areata using ciclosporin . In the case of dogs, the comorbidity of dermatophyte infections and metabolic diseases has been described . Clear predispositions were noted when hyperadrenocorticism was diagnosed [52, 110]. Other described cases of co-occurring dermatomycoses concern Yorkshire Terrier dogs with diabetes, as well as leishmaniasis and/or erlichiosis . Dermatomycosis has also been diagnosed in dogs with demodicosis, however, only one publication describing such a case is available . According to the authors, such comorbid infections are more common than might be expected if the state of being an asymptomatic carrier is also taken into account.
Animal breeders and veterinarians express their conviction regarding certain breeds of dogs and cats being highly sensitive to dermatophyte infections. Scientific reports do not expressly confirm the correlation between the breed and the prevalence of dermatomycoses, and all information on breed-related predilections is solely the domain of suppositions. One of the most often-mentioned breeds of cats which are highly sensitive to dermatophyte infections are Persian cats. Scott et al. found that 75% of the cases of dermatomycoses diagnosed in cats at the Small Animal Clinic at the University of Montreal was related to Persian cats, but the total number of diagnoses made during this period only amounted to four cases . Similar observations were made by Lewis et al.; in the conducted studies, 61 cases of dermatomycoses were diagnosed, of which 15 were present in Persian cats . However, it should be mentioned that Persian cats were overrepresented in this study because they constituted 5% of all the cases related to cats at the veterinary clinic, but as much as 24.6% of cats with skin mycosis . Similarly to the description of a study from the United Kingdom , in reports on dermatological treatment, case reports concerning Persian cats also constitute the most numerous group out of all the reports, which may additionally suggest that the prevalence of dermatomycoses in this breed is high [8, 11, 22, 23, 59–62, 80, 81, 86, 103, 108]. The first attempts to use griseofulvin in treating dermatophyte infections was related precisely to Persian cats, whereas in the examination of itraconazole’s pharmacokinetic and pharmacodynamic properties, Persian cats constituted a substantial portion of every study group [61, 62]. Descriptions of cases related to subcutaneous infections caused by dermatophytes have been recorded almost exclusively in longhair breeds, particularly in Persian cats [8, 11, 22, 60, 80, 81, 103, 108].
Some breeds of dogs also seem to be predisposed to the occurrence of dermatophyte infections. In the scientific literature, several descriptions of cases are available were dogs of the Yorkshire terrier breed were classified as predisposed towards surface and subcutaneous fungal infections caused by M. canis [7, 16, 20, 107]. On the basis of studies conducted by them, Cafarchia et al. report that out of 55 dogs with a dermatophyte infection, as many as 13 (23.6%) of them were dogs of the Yorkshire terrier breed , while Brihante et al. diagnosed dermatomycosis in 27 dogs, out of which as many as 10 (37%) belonged to this breed . This is not the only breed of dogs with a high prevalence of symptomatic dermatophyte infections. Dogs of hunting and working breeds, i.e. German shorthaired pointer, wire fox terrier, labrador retriever, groenendael, beagle, pointer, Jack Russell terrier, German shepherd and jagdterrier also seem to be predisposed towards dermatomycoses, especially those caused by geophilic fungi such as M. persicolor (Guiart & Grigoraki 1928) and M. gypseum (Guiart & Grigoraki 1928), probably due to their increased contact with soil containing arthrospores [11, 20, 78].
Arthrospores, which are propagules of asexual reproduction created as a result of the fermentation of a fungus’ hyphae, are believed to be an infectious form of dermatophytes [76, 77, 78]. Two routes of transmission have been described in the literature for arthrospores: the direct and the indirect one . The former refers to the direct contact of an infected specimen, including an asymptomatically infected one, with a healthy animal . Indirect transmission includes the possibility of transferring arthrospores onto a healthy specimen through tools for skin care and fur care, bed linen, collars and other utensils in contact with the animal and individuals infected with dermatophytes [42–44, 106]. In each of these cases, micro-injuries to the skin are an important factor in developing the infection .
In dermatomycoses caused by M. canis, the transmission route is usually the contact with an infected animal, mainly a cat, or with contaminated utensils for animal care . In 2018, our team demonstrated  that the incidence of M. canis infections in animals whose skin had been damaged is usually higher in cats than in dogs, and over 90% of feline and 75% of canine skin lesions are aetiologically related to this fungus. In the case of infections caused by zoophilic species of the Trichophyton genus, recent scientific reports indicate that direct and indirect transmission is associated with coming into contact with infected rodents or their habitats . Moreover, faeces of rats or other wild rodents left in places to which animals have access, and even insects which have come into contact with these faeces, are enumerated among arthrospore vectors [25, 43]. Indicating the source of infection is much easier in the case of the less common geophilic dermatophytes. M. gypseum infections are caused by coming into contact with contaminated soil, especially in places where rodents have their burrows and holes [35, 44]. Other mentioned reasons that create good conditions for the development of dermatophytes also include microinjuries to the skin of animals, due to the itching sensation that occurs then, as well as increased humidity and invasions of ectoparasites . The importance of micro-injuries in the development of dermatomycosis has been confirmed in vivo. When causing a dermatophyte infection in laboratory conditions, one of the requirements was that the surface of the skin should be slightly mechanically damaged and kept moist at all times before the incubation of the fungus . Additionally, cats’ behaviour of grooming themselves is probably one of the defence mechanisms against a skin infection . Causing a fungal infection in laboratory conditions as part of an experiment was difficult to achieve precisely because cats groomed themselves, getting rid of arthrospores from the surface of their skin and fur in this way. This necessitated the use of Elizabethan collars in the studies, which prevented grooming . Only then did symptoms of dermatomycosis develop in vitro.
The mechanism of a dermatophyte infection is not yet fully understood, but we may distinguish three main stages in it. At the outset, it should be noted that the clinical picture of dermatomycosis, the degree of the symptoms’ expression and their severity will be based on factors that are mainly dependent on the immune condition and sensitivity of the host organism and the virulence of the fungus itself [5, 6, 35]. The moment when arthrospores adhere to the corneocytes in the stratum corneum of humans and animals should be considered as the first stage of the infection’s developement [41, 104]. Scientific reports indicate that this first stage of pathogenesis lasts from four to six hours, and its mechanism is based on the interaction of electrostatic forces between specific adhesins on the surface of arthrospores and corneocytes [5, 37, 104]. Factors which are important in this process include: the optimal temperature (25–35°C), high humidity (80%) and an acidic reaction (5.5–6.7) [4–6, 37, 104]. Proteases specific to particular species. e.g. subtilisins, also play an important role here . The second stage of the pathogenesis of a dermatophyte infection is the germination of arthrospores . In vitro studies have demonstrated a different spore germination time in infections with zoophilic dermatophytes in animals and humans. In a model using animal corneocytes and T. mentagrophytes isolates, spore germination occurred within 4 to 6 hours from the moment of coming into contact, while in the case of a model with the human epidermis, it only occurred after 24 hours [2, 41]. It is assumed that the moment when the mycelium starts to grow into the stratum corneum marks the end of this stage of pathogenesis [34, 35]. The third stage is the penetration of the fungus into the host’s keratinized structures . The growth of the mycelium is most often multi-directional, which correlates with the speed at which the infection spreads . Within 7 days from the moment of the arthrospores adhering to keratinocytes, the fungus’ hyphae begin to create arthrocondia, thus closing out the life cycle of the fungus . From that moment on, the infection becomes contagious, in spite of the fact that in the vast majority of cases, it still remains asymptomatic [2, 34, 35]. The first clinical symptoms usually appear between one and three weeks after the exposure to arthroconida [2, 30, 34].
Dermatophytes’ virulence factors include various exoenzymes, among which keratinase, protease, lipase, phospholipase, gelatinase, DNase and haemolysines are most often enumerated, which are responsible for supplying pathogens with nutritional substances and ensuring that they remain in the host’s stratum corneum [35, 39, 87]. Reports from recent years indicate that these enzymes are characterized by their high substrate specificity, which determines the spectrum of hosts in particular species of dermatophytes . The released enzymes act as antigens which induce and model the inflammation [31, 87].
The best-studied group of dermatophytes’ enzymes, considered by many scientists to be the main virulence factor involved in the invasion into the cornified layers of the epidermis and using them as a source of nutritional substances, are proteases [39, 40]. Presumably, protease secretion is stimulated by some components of the nurturer’s epidermis over the course of the dermatophyte’s invasion . Some authors suggest that dermatophytes secrete proteases to facilitate adhering to the host’s tissue, and even that they may be necessary for this process to take place . The proteolytic activity of dermatophytes results from their ability to secrete various enzymes which, both as endoproteases (subtilisins and fungalizins) and as exoproteases (the S peptidase and serine proteinase), allow pathogens to break keratin down into peptides and amino acids [28, 39, 40]. The degradation of keratin is accompanied by the simultaneous reduction and scission of disulphide bonds which connect keratin filaments to the amino acids cysteine and selenocysteine [65, 66]. This process is possible due to the activity of the sulphite pump encoded by the SSU1 gene . Regulating the formation of sulphite from cysteine is another important virulence mechanism, one that relies mainly on the activity of cysteine dioxygenase (Cdo1) . Although it is obvious that proteolytic activity is crucially important for the degradation of structures with a compact keratin structure, proteases themselves are not able to dissolve keratin elements that are rich in cysteine [50, 66]. It seems that the pattern of proteolytic decomposition caused by dermatophytes is specific to the infected species and determines the range of sensitive hosts , while also indirectly affecting their immune response . In addition to the secretion of proteolytic enzymes, other mechanisms of influencing the host’s immune response also include extra-enzymatic factors, i.e. inhibiting the activity of lymphocytes by means of mannans found in the cell wall of fungi, changing the activity profile of macrophages or influencing the speed at which keratinocytes are exchanged [26, 45, 104].
Lipases are another group of enzymes involved in the development of symptomatic dermatophyte infections. These enzymes are important for the survival of pathogens on the surface of the skin before the fungi penetrate into the lower layers of the epidermis which are richer in proteins . Lipases make it possible for dermatophytes to use lipids as their primary source of carbon . Interestingly, on the surface of the skin, there are fatty acids that originate from the hydrolysis of fats by bacteria and some of them, particularly those with a molecular mass close to undecylenic acid, have fungistatic properties . They are often used in antifungal therapy . The discrepancy between the effect of the fatty acids present on the host’s skin inhibiting the growth of fungi on the one hand and the possibility of the skin’s lipids being used by pathogens as nutritional substances on the other may be explained by the self-regulatory mechanism of fungal lipolysis. The activity of the lipases produced by dermatophytes is inversely proportional to the amount of fatty acids released because these enzymes are rendered inactive by an excess of fatty acids . Presumably, the lipolytic activity of zoophilic dermatophytes, especially M. canis, is responsible for the formation of annular lichen planus on the skin of animals .
The phenomenon of haemolysis triggered by proteins produced by dermatophytes plays an important role in the balance between the host’s cell resistance and the ability of the fungus to reduce the immune response . It has been demonstrated that the haemolytic activity of dermatophytes correlates with the severity and chronicity of clinical lesions resulting from dermatomycosis . The mechanism of dermatophytes causing the lysis of erythrocytes has not yet been fully understood. It is believed that this activity is associated with secreting lipases and phospholipases outside of the cell, which may damage the membranes of erythrocytes . On the other hand, the activity of phospholipases evaluated in vitro does not explain the formation of haemolysis. It has been demonstrated experimentally that the addition of purified fungal phospholipases to a suspension of erythrocytes does not cause their lysis [39, 92]. Probably, the effect of an additional, unspecified factor is needed . The research carried out thus far has not given any reason to indirectly associate the enzymatic activity of dermatophytes with the triggering of haemolysis [17, 18, 39, 92]. Interesting observations related to the occurrence of haemolysis have been made for some species of dermatophytes, i.e. T. rubrum, T. equinum and T. verrucosum. For clinical isolates of these dermatophytes, haemolysis was defined as double, i.e. with a site of complete haemolysis around the fungus’ colony and a site of incomplete haemolysis a few millimetres away from it [39, 43, 92]. The phenomenon of double haemolysis may indicate the secretion of two different cytolytic factors by these dermatophytes . In principle, significantly weaker haemolytic activity was noted for anthropophilic dermatophytes, as well as for fungi of the Microsporum and Epidermophyton floccosum genera .
DNases are a little-studied virulence factor in dermatophytes. In scientific research, it has been found that dermatophytes isolated from chronic cases demonstrated a high activity of deoxyribonucleases . Meanwhile, isolates obtained from clinical lesions in severe cases of the disease demonstrated a low in vitro activity of this enzyme . On this basis, a conclusion was drawn that DNase plays no role in the formation of skin lesions, but may promote the development of the infection in its initial phase . Elastase is another widespread virulence factor of dermatophytes. The production of this enzyme by dermatophytes is associated with a strongly marked inflammation and, in the case of T. mentagrophytes, with the appearance of lesions on the skin of animals . It has been demonstrated, however, that the activity of elastase marked in vitro in M. canis is significant in isolates from humans, but negligible in animal strains [17, 39].
The clinical symptoms of an infection are an external reflection of the functioning of dermatophytes’ virulence factors. Due to the extraordinary predisposition of dermatophytes towards the decomposition of keratin, the most common symptoms of their development include: hair loss, the formation of papules, scales, scrubs, erythemata and discolouration of the skin and changes in the appearance of nails [41–43, 106]. These lesions usually appear asymmetrically . Pruritus, in turn, should be treated as a symptom that may or may not occur depending on the particular disease . In the case of cats, regardless of their breed, due to its irritating nature, pruritus may be a symptom of both dermatophytosis as well as pyodermatitis, or the eosinophilic syndrome . Clinical lesions in cats initially appear around the eyes, on the ears and around the mouth, and then spread in the direction of the limbs [29, 38]. Due to the similar symptoms, a differential diagnosis of dermatophytosis in cats should include an inflammation of paw pads and general exfoliative dermatitis . It should be noted that examinations of the fur of cats which had been subjected to treatment as a consequence of an often long-lasting dermatophyte infection may yield a false negative result for fluorescence in Wood’s lamp . This constitutes an important argument for the necessity of performing mycological identification tests in every case.
Dermatomycoses in dogs may take the form of lumps more rarely than in cats [23, 24]. In such cases, identifying the aetiological factor of a fungal infection is difficult, and the diagnosis is based on a cytological examination of a fragment of the lesion or an aspiration from a fine-needle biopsy [7, 8, 10, 22–24, 60, 80, 81, 103, 108]. In the case of dermatophyte infections which take the form of lumps, the most represented breeds include Persian cats and dogs of the Yorkshire terrier breed . In the clinical picture, from one to several subcutaneous lumps are usually observed [8, 11, 108]. A kerion, which may take the form of singular or numerous lumps with a semi-spherical cross-section with co-occurring hair loss or an inflammation, is one of the varieties of nodular lesions in dogs. A histopathological examination of this type of lesions reveals granulomas with fragments of hair containing spores of fungi . A diagnostic examination using Wood’s lamp in dogs with a kerion is very often misleading. Cornegliani et al. have demonstrated that the examination of the fur of dogs with a kerion in the course of dermatophytosis (n = 23) yielded a negative result of fluorescence in Wood’s lamp, and, in the direct examination of the coat, arthrospores were only found in eight of the dogs. Meanwhile, for 21 of the dogs participating in this study, a cytological examination demonstrated the biggest identification strength, enabling the diagnosis of the fungus . In cases of pseudomycetomata and mycetomata, which appear more rarely in the course of dermatophytosis in dogs, the lumps have the nature of ulcers with a seropurulent discharge rich in inflammatory cells seeping out of them. A superficial mycosis which takes the form of pustules is described sporadically in dogs and may histologically imitate pemphigus foliaceus [85, 88]. It should be noted that in all of the listed cases, the simultaneous performance of a cytological examination and inoculation of a culture on a mycological medium is important, as this enables isolating the pathogen’s strain.
Such a large variation in the clinical symptoms of dermatomycosis may be related to the host’s response to an inflammation, as well as the response of its immune system. In animals with other comorbid skin diseases, the lesions’ nature is multifocal and they are scattered across the entire body [7, 91, 103]. Polak et al. have stated that the occurrence of multifocal dermatophyte infections in cats is much more frequently diagnosed in urban centres. Most likely, the factor that predisposes an animal to developing such forms of dermatomycoses is the long-lasting exposure to the effects of stress . In hunting dogs, meanwhile, multifocal lesions appear on the muzzle and the head due to coming into contact with the soil, thus directing diagnostic examinations towards geophilic dermatophytes [10, 20]. If it is a nail that is affected, its onychogryphosis and discolouration may be observed .
The immune response to a dermatophyte infection constitutes a combination of the effect of specific antibodies and the humoral response . However, completely curing a disease and protecting against contracting it again is largely dependent on the efficient cellular immune response, which encompasses the activity of effector cells, i.e. macrophages and neutrophils, as well as the interferon gamma (IFNγ) [98,104]. Interestingly, some species of dermatophytes have the ability to avoid the host’s immune response, which has been described in cases of chronic infections . In specimen infected with T. rubrum, due to mannans of the fungus’ cell wall, immunosuppression occurs by means of inhibiting the activity of leukocytes with a non-segmented nucleus . In addition, the direct contact between T. rubrum conidia and macrophages results in the production of the tumour necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and nitric oxide by these immune cells, which, in turn, leads to the death of the macrophage .
Lorenz et al. have demonstrated that IgG, IgA and IgM antibodies do not perform any essential role in dermatophyte infections . In cats with symptomatic mycosis caused by M. canis, immediate and delayed intracutaneous reactions were observed in response to the administration of dermatophytes’ proteins . The main changes recorded after the administration of a fungal antigen included an increased antibody titer and proliferation of limphocytes . It has been demonstrated that cats who had previously contracted an M. canis infection were characterized by a significantly higher activity of lymphocytes relative to skin antigens in comparison to cats which had never been ill before [21, 31]. Meanwhile, a similar activity of lymphocytes has been recorded in cats which were suffering from dermatomycosis at that moment and in those which had contracted the infection before [19, 31]. Meanwhile, antibody titers in the group of cats which were affected by the disease at that moment was significantly higher compared to specimens that have already been cured from dermatomycosis [19, 68].
Dermatophyte infections are mostly transmitted by coming into contact with the fur of skin lesions of an infected animal, the care products and toys with which it has contact, as well as by asymptomatic carriers. The accumulation of skin flakes and animal fur in the environment constitutes a likely source of infection for humans. Dermatophytosis is a common skin disease in people with a weakened immune system; nevertheless, an overview of the literature indicates that it is T. rubrum which is the aetiological factor of the infections in humans and not M. canis, which is most often isolated from pets. In spite of the fact that dermatophyte infections may be cured using commonly available antibiotics and chemotherapeutic agents, the treatment is prolonged and the symptoms often recur. In such cases, identifying the source of an infection should be an important goal of the diagnostic examination, and dogs, cats and other domestic animals should always be taken into account.