Germ tube production of Candida albicans is favoured by, and is adapted to, conditions of nutrient deprivation, particularly low nitrogen. Hyphal development in media containing low serum concentrations is characterised by the formation of sparsely branched hyphae in which uninucleated, highly vacuolated intercalary compartments are arrested in the cell cycle, probably in G1. Re-entry into the cell cycle is accelerated by enrichment of the medium for nutrients and is preceded by reduction of the vacuolar space and concomitant increase in the size of the cytoplasmic volume. Hyphae exhibit contact guidance (thigmotropism) which may facilitate the invasion of tissues through local wounds, invaginations or sites of weakened surface integrity. Thus hyphal growth is adapted for nutrient scavenging and penetration of irregular surfaces.
The genetics of dimorphism and virulence has been investigated through studies of differential gene expression, and by specific manipulation of gene expression by overexpression and the creation of null mutants. The expression of many genes is regulated during dimorphism however few of these play active roles in the regulation of morphogenesis. Disruption of genes encoding certain secreted aspartyl proteinases (SAP2) and a key step in the assembly of O-linked mannosylation (MNT1) led to attenuation of virulence. Manipulation of the expression of a hyphal specific gene HYR1 did not affect germ tube growth while overexpression of a constitutively expressed Candida gene HST7 stimulated pseudohyphal growth in Saccharomyces. Therefore, analysis and manipulation of the normal temporal pattern of gene expression is yielding valuable information regarding the regulation of morphogenesis and pathogenesis in this fungus.

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Mucocutaneous manifestations of fungal disease are quite common in immunocompromised patients. The most frequent fungal infections include dermatophytoses of the skin and nails, candida and seborrheic dermatitis. Cryptococcosis, histoplasmosis and coccidioidomycosis are seen less commonly and when mucocutaneous surfaces are involved, it is in the setting of disseminated fungal disease. These infections may vary greatly in their clinical presentation and the appearance is often atypical. Thus it is essential to biopsy and culture the skin lesions of these patients whenever the diagnosis is uncertain. The high recurrence rate of fungal infections in human immunodeficiency virus-positive patients requires the use of long-term suppressive maintenance therapy. The emergence of newer antifungal agents has provided additional treatment alternatives.

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The fungicidal activity of human natural antibodies, elicited in the course of Candida albicans and Pneumocystis carinii infections against the cell wall receptors for a Pichia anomala killer toxin, that mimic the yeast killer toxin-like antiidiotypic antibodies (antibiobodies) raised through parenteral and mucosal immunization with a yeast killer toxin neutralizing monoclonal antibody (idiotypic vaccination) which protected animals from systemic and vaginal candidiasis is discussed on the basis of the background of the yeast killer phenomenon and in the perspective of the potential of molecular immunology for the production of conceptually new engineered antifungal recombinant antibodies.

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The adhesion of Candida albicans to host tissue is thought to be important in the development of candidiasis. Since the isolation frequency of C. albicans serotype A (A) from clinical specimens is significantly higher than that of C. albicans serotype B, a seratype A-specific antigen, designated antigen 6, which resides in mannans on the cell surface, is assumed to be significant in the adhesion of C. albicans A. To determine the role of the antigen 6 in adhesion of the organism to human epithelial cells, we used antigen 6-deficient mutants which had been isolated by screening with an agglutinating monoclonal antibody against antigen 6 (MAb-6). The mutant yeast cells exhibited significantly reduced ability to adhere to a human buccal cell line. Moreover, the whole mannan from the C. albicans A parent as well as polyclonal and monoclonal antibodies specific for antigen 6 inhibited the adhesion of C. albicans A parent to the cell line. Furthermore, all of the strains which bear antigen 6 exhibited significantly higher adhesion to the cell line than that of the strains which lack antigen 6. These results suggest that antigen 6 is largely involved in the adhesion of C. albicans A to human epithelial cells. On the other hand, the reaction between parent whole mannan and MAb-6 was inhibited by acetolyzed oligosaccharides which possess terminal β(1-2) linkage (s) but not by those which lack the β-linkage. The conformational analysis by hard-sphere exo-anomeric calculations indicated that the conformation of mannooligosaccharide which possesses one terminal β-linkage was significantly resemble to that of O-side chain of Salmonella serogroup C₁, which reacts with MAb-6, suggesting that the structure of determinant against MAb-6 is Man-β(1-2)-Man-β(1-2)-Man-. Taken together, these results suggest that as far as mannan adhesin is concerned, the mannan side chain reactive with MAb-6 is a predominant ligand for adhesion of C. albicans A to human epithelial cells.

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Secreted aspartyl proteinase from C. albicans is known as a pathogenic factor which degrades host tissues during the invasion process. Recently genes encoding SAP have been cloned, and their regulation mechanism is now being extensively investigated. During the process of investigating the various effects of SAP, we observed that SAP has a chemotactic activity toward neutrophils. The chemotactic activity of SAP was then examined by a modified Boyden chamber method using normal human peripheral leukocytes. SAP showed dose-dependent chemotactic activity for neutrophils with maximal activity at 500nM. Little chemotactic activity was observed for peripheral lymphocytes. Checkerboard analysis indicated that SAP is chemokinetic as well as chemotactic for neutrophils. SAP-injected guinea pig skin indicated significant infiltration of neutrophils. These results suggest that SAP, which theoretically acts as a host tissue-degrading enzyme, induces the migration of peripheral neutrophils to the C. albicans-infected site.

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Postmortem infectious lesions were analyzed in 63 patients with bacteremia and fungemia. Bacterial infection was found in 36 patients, deep mycoses in 27 and cytomegalovirus infection in 7. Among deep mycoses patients, yeast was noticed in 17, Aspergillus in 13 and Mucor in one. Infectious lesions were not observed in 10 cases. Fifteen cases of 23 leucopenic patients were complicated with deep mycoses.
Deep mycoses was noticed in 43% of bacteremia and fungemia patients, but not in candicemia patients. Fungemia due to Candida was related to blood access, however, not to deep mycoses. On the other hand, disseminated mycoses was found in 4 of 5 cases with Trichosporon beigelii fungemia. T. beigelii infection is noticeably life-threatening to the immunocompromised host.

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The present study dealt with a new polymerase chain reaction (PCR) primer system using a primerpair constructed of conserved DNA sequences of 18S-rRNA genes to detect a wide range of medically important fungi, and subsequent Southern analysis of the PCR-amplified products for species or group-level identification. This system was successfully applied to blood specimens from the murine model of invasive candidosis and to clinical specimens from human cases of deep mycosis.

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The role of tumor necrosis factor alpha (TNFα) and gamma interferon (γINF) in host defense against systemic Candida albicans infection was evaluated in a murine candidiasis. Administration of anti-TNFα monoclonal antibody shortened survival of mice inoculated with C. albicans intravenously, suggesting that endogenous TNFα plays a protective role in host resistence to Candida albicans infection. With this regimen, colony counts of left kidney were significantly higher in anti-TNFα MoAb recipients. In contrast, injection of anti-γINF MoAb did not accelerated death of mice with systemic candidiasis. Thus, endogenous TNFα and γINF play different roles in C. albicans infection.

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Efficacy of random amplification of polymorphic DNA (RAPD), a polymerase chain reaction (PCR)-based technology, as a molecular taxonomic marker for differentiation between Trichophyton (T.) mentagrophytes (m.) var. interdigitale and T. rubrum was examined. Total cellular DNAs were extracted from four clinical isolates of T. m. var. interdigitale and T. rubrum, and were used as template DNAs. By using 6 of 9 primers, which had been synthesized 10-mers, characteristic sets of PCR-products for each species were obtained. A minimal degree of intraspecies polymorphism was observed between the isolates of T. rubrum. The results suggest that RAPD using these 6 primers is useful to differentiate between these dermatophyte species.

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In studies on the isolation of fungi from the skin and scalp normal-looking skin was mycologically cultured by the cotton swab method or the finger-press method, and the scalp was cultured by the hairbrush method. Patients on oral steroids and with cutaneous- or muco-candidosis, blood disease, internal disease (diabetes mellitus, malignancy, collagen disease), or cutaneous infectious disease were compared with healthy controls. Candida albicans was isolated from the skin of 15 of 26 patients (57.7%) with cutaneous- or muco-candidosis, but was not detected on 28 healthy controls; it was also isolated from 2 of 19 patients with blood disease. The rate of detection of other fungi (Aspergillus spp., Penicillium spp., black yeasts, other molds, and other yeasts) from the skin and scalps of patients with blood disease was mach lower than those of other patients and controls. Most fungi except C. albicans were more frequently isolated from the scalp than the skin. Therefore, it can be concluded that the focus of fungi colonized on the skin was the scalp; since patients with blood disease had little or no hair due to their chemotherapy, few fungi adhered their scalp, accounting for the much lower detection rate.

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Clinical isolates from superficial trichosporonosis patients were identified on the basis of DNA relatedness. Trichosporon cutaneum, T. mucoides and our new proposed species, T. domesticum were found in the clinical samples. These findings suggest that the causative agents of superficial trichosporonosis exist in three or more species, and are different from those of deep-seated and mucosa-associated infections.

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We report the case of a 78-year-old housewife with candida paronychia·onychia of a toe. The patient has suffered for a number of years from bronchial asthma. and has occasionally been intravenously injected with corticosteroid. On June 10, 1995, she visited our department because she developed erythema with slight swelling and dull pain on the nail fold of her left big toe. During the month prior to her visit, she was treated with antibiotics for hemoptysis, and few weeks later, the tip of the left big toe became diffusely swollen. She noticed an increase in pain, although sharp pain lessened spontaneously after the wound discharged pus three or four days before she visited us. The toe exhibited slight erythema and swelling with dried pustules. Marked exfoliative scales were present in the nail cuticle and the nail glove. Numerous fungal elements of hyphae and grape-shaped spores were detected in the scales and nail plates of the lesion by a direct examination using the KOH method. Organisms isolated from the lesions were identified as Candida albicans serotype A, although no bacteria was cultured. The leisons completely disappeared after 7 weeks therapy with topical application of an antifungal reagent.
To our knowledge, only 4 cases of candida paronychia·onychia of the toe have been reported in Japan. We suspect our case to have been complicated with bacterial paronychia.

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