Early Events in the Invasion of Skin, Nail and Hair by Dermatophyte Fungi

Rashid, Azer (1993) Early Events in the Invasion of Skin, Nail and Hair by Dermatophyte Fungi. PhD thesis, University of Glasgow.

Abstract

The early events in the invasion of keratinized tissues (stratum corneum, nail and hair) by dermatophyte fungi were investigated by employing arthroconidia of two strains, one of Trichophyton interdigitale and one of Trichophyton mentagrophytes. New in vitro experimental model systems were employed to study the colonization of these tissues by dermatophyte fungi, including the germination and hyphai extension of such fungi, and their response to antifungal agents. The germination of arthroconidia and hyphai extension on different body surfaces (face, back of the hand, palm, leg and sole) was determined by using stripped sheets of stratum corneum from these areas. The ultrastructural relationship between arthroconidia and germ tubes while growing on the stratum corneum was investigated by scanning and transmission electron microscopy. The possibility of using this stratum corneum model for assessing antifungal drugs was explored by pre-exposing the corneocytes to therapeutic concentrations (6.2-100 mg/L) of terbinafine and assessing the effect on germination and hyphai extension of T. interdigitale arthroconidia. The morphological changes induced by terbinafine in the arthroconidia and germ tubes of T. interdigitale whilst growing on the stratum corneum were also observed. The morphological transformation of dermatophyte arthroconidia on nails was studied by using distal nail clippings (finger, toe) and observing the process of nail invasion by germ lings of T. mentagrophytes in the absence of added nutrients with scanning and transmission electron microscopy. This nail model was used to assess the antifungal activity of terbinafine against dermatophytes by pre-exposing the nails to low concentrations (0.001-10 mg/L) of terbinafine and then studying its effects on the germination and hyphai extension of T. mentagrophytes arthroconidia. At the same time observing morphological changes in the growth forms, growing on terbinafine-exposed nails with scanning and transmission electron microscopy. A novel hair model was explored for detailed study of the invasion of hair and the effects of antifungal drugs on the invasion process by dermatophyte fungi. This was achieved observing the morphological transformation of T. mentagrophytes arthroconidia on dissected human terminal hair follicles and plucked anagen hair maintained in organ culture. These were then exposed to low concentrations (0.01-10 mg/L) of terbinafine and determining the effect on germination and hyphal extension and morphological changes induced in these growth forms. This whole process was studied with light microscopy and by scanning and transmission electron microscopy. Similarly, the human living skin equivalent was utilised to examine the establishment and growth of T. mentagrophytes arthroconidia, and to subsequently assess the effects of terbinafine. Germination and hyphal extension of arthroconidia was studied on the living skin equivalent. Low concentrations of terbinafine (0.01-10 mg/L) were incorporated in the model. The effect on fungal growth was examined histologically using haemoJoxylin and eosin - and periodic acid/schiffs (PAS) stained sections and by scanning electron microscopy. Germination of T. interdigitale arthroconidia was observed on all body surfaces (face, back of hand, palm, leg and sole). 100% germination of arthroconidia occurred on face and back of hand and leg while 80-95% germination was seen on palm, leg and sole by 24h. Hyphal extension was observed on all the body surfaces. There was a direct relationship between percent germination and hyphal extension on face, back of the hand and leg and an inverse relationship on palm and sole. A mycelium was in place at most of these sites by 48h. Close adherence of arthroconidia and germlings was confirmed by scanning and transmission electron microscopy. A fibrillar- floccular material bridged the intercellular space between the arthroconidial wall and the surface of the corneocytes. A mixed picture of germinated and ungerminated arthroconidia and germ tubes of various lengths was seen, with the appearance of side branches and secondary germlings. Germ tubes and side branches were observed growing on and in the direction of corneocytes. It appears that factors present in corneocytes are crucial for the establishment of dermatophyte infection on the stratum corneum. Germination of arthroconidia was partially inhibited by therapeutic terbinafine concentrations though hyphal extension was totally inhibited on the body surfaces. Dose dependent morphological changes were observed in the arthroconidia and germ tubes. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: R M Mackie
• Keywords: Medicine, Pathology
• Date of Award: 1993
• Depositing User: Enlighten Team
• Unique ID: glathesis:1993-75612
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 19:17
• Last Modified: 19 Nov 2019 19:17
• URI: https://theses.gla.ac.uk/id/eprint/75612