Several pink or dark brown mutants of Candida albicans were obtained following exposure of the wild types to ultraviolet irradiation or ethyl methanesulfonate. Unlike the wild types, all the mutants required adenine and in addition the dark brown strain required valine and isoleucine for growth. The mutants accumulated the pigment in the cytoplasm either as localized granules or in a diffused form. They, however, did not differ from their parental strains in size and shape of yeast cells, fermentation and assimilation of sugars. Initially, the pink mutants were more resistant to amphotericin B, but upon passage on agar media for a prolonged period, they became as sensitive as the wild types. The pink strain produced less mycelium in vitro and in vivo, and were less virulent for mice, but more resistant to ultraviolet irradiation than the wild types.
Scanning electron microscopy of four different Paracoccidioides brasiliensis isolates in the yeast phase revealed that mother cells generating multiple, spherically shaped buds may be firmly or tenuously associated with their progeny whereas elongated buds remain attached to the mother cell through stem-like structures and may represent early stages of hypha formation. The yeast cell surfaces were covered with a delicate network of microfibrillar components.
Cerebrospinal fluid from rabbits with chronic cryptococcal meningitis was tested for its chemotactic activity towards polymorphonuclear cells and monocytes. CSF chemotactic activity was present; it peaked 5-8 days after infection, coinciding with the time when the number of inflammatory cells in CSF was greatest. However, little chemotactic activity could be found in the early stages of infection, during the initial ingress of inflammatory cells. The chemotactic activity appeared to be host-derived, with characteristics consistent with lymphokine(s) or C5a. Treatment with cortisone significantly reduced the CSF chemotactic activity for both cell types; this reduction may contribute to the severe CSF leukopenia observed in cortisone-treated animals, which are unable to eradicate this yeast infection. Modulation of CSF chemotactic activity may be important to the success or failure of the host central nervous system response to Cryptococcus neoformans.
Unbudded singlets from exponentially growing yeast cells of Sporothrix schenckii were harvested, selected by filtration and allowed to form germ tubes in a basal medium with glucose at pH 4.0 and 25 degrees C. These conditions supported only the development of the mycelial form of S. schenckii in a reproducible manner which allowed further analysis of the early cellular events occurring during the yeast-to-mycelium transition. The relationship between macromolecular synthesis (DNA and RNA synthesis) and nuclear division, hyphal growth and septum formation were investigated during germ tube formation. RNA synthesis started 0 to 3 h after the induction of germ tube formation, followed by DNA synthesis and the first nuclear division, which took place between 3 and 6 h. Germ tube formation followed nuclear division and was first evidenced 6 h after the induction of germ tube formation, but was not completed until 12 h after inoculation. Septation was first observed in these germ tubes at the mother cell-germ tube junction 6 h after induction. Addition of hydroxyurea, an inhibitor of DNA synthesis, to the medium, also inhibited nuclear division and germ tube growth, suggesting that these processes in S. schenckii are dependent upon DNA synthesis.
Scanning electron microscopy of four different Paracoccidioides brasiliensis isolates in the yeast phase revealed that mother cells generating multiple, spherically shaped buds may be firmly or tenuously associated with their progeny whereas elongated buds remain attached to the mother cell through stem-like structures and may represent early stages of hypha formation. The yeast cell surfaces were covered with a delicate network of microfibrillar components.
An inhibition ELISA method was used to test culture filtrate antigens of Aspergillus fumigatus for the avidity of antibodies to them. Four different culture media were used to check the ability of this assay to distinguish between similar antigenic preparations. Differences between antigens exhibiting similar crossed immunoelectrophoresis patterns were observed by inhibition ELISA.
In the past, the rat model of experimental vaginal candidosis has been used to study the efficacy of antifungal agents in eradicating acute vaginitis. In the present study, chronic vaginal candidosis was induced to study the natural history of the infection. Results indicate that chronic infection is readily achieved and is strictly dependent on oophorectomy and hormonal maintenance of pseudoestrous. Histologic studies confirm that rats so infected and with long term vaginal carriage of Candida albicans have true chronic infection with extensive mycelial formation and superficial mucosal invasion.
SF 86-327 (Sandoz Forschungsinstitut) is an orally active allylamine derivative related to naftifine. The antifungal activity of SF 86-327 was compared in vitro with those of naftifine, ketoconazole, and itraconazole (R 51,211, Janssen Pharmaceutica) by agar dilution. 120 fungal isolates were tested. Also, the antifungal activities of SF 86-327 and naftifine against 18 dimorphic pathogens were assayed in vitro by broth dilution. Results of these studies support claims that SF 86-327 is a broad spectrum antifungal agent. Results of the broth dilution studies also revealed that SF 86-327 was both fungistatic and fungicidal in vitro for isolates of Blastomyces dermatitidis, Histoplasma capsulatum and Sporothrix schenckii at concentrations as low as 0.05 micrograms ml-1 (18 isolates tested, MIC90 = 0.39 micrograms ml-1, MFC90 = 12.5 micrograms ml-1).
C5-deficient (C5-) mice succumb much sooner after intravenous inoculation with Cryptococcus neoformans than do C5-sufficient (C5+) mice. The C5- mice developed acute, fatal cryptococcal pneumonia, whereas the C5+ mice did not. The pneumonia was characterized by lung viable counts in C5- mice up to 1000-fold higher than in C5+, initial sequestration of twice as much 59Fe-labeled C. neoformans, and subsequent development of pulmonary edema. Chemotaxis of heterophils (PMNs) and mononuclear cells in response to C. neoformans was markedly greater in C5+ mice than in C5- animals. The effect of C5 on localization and growth of C. neoformans in the lung appeared to account for the disparate survival times of C5+ and C5+ mice after intravenous inoculation with C. neoformans.
Ninety-six patients with clinical evidence of interdigital lesions classified as mild, moderate and severe athlete's foot were investigated for bacterial and fungal populations in the interspaces. Gram-negative bacteria, which were not found in the toe spaces of 50 normal controls, were grown in increasing numbers and with increasing frequency as the symptoms progressed from mild to severe. Gram-positive bacteria were also isolated regularly and in increasing numbers commensurate with the severity of the disease. Similarly the isolation rates of dermatophytes and Candida species were higher in patients with moderate and severe disease compared to those with mild disease. Clinical and culture responses to topical applications with framycetin, tolnaftate, miconazole and clotrimazole were also studied. In some patients the prevalence of pathogenic fungi increased as bacterial numbers decreased. The pure antibacterial framycetin brought symptomatic relief, as did the purely anti-dermatophyte substance tolnaftate, but best results were seen with two azole compounds having mixed antibacterial and antifungal properties.
Investigations on the chemotaxis of polymorphonuclear neutrophils (PMNs) towards a cytoplasmic extract of Trichophyton rubrum in the presence and absence of antifungal drugs are described. It is shown that with griseofulvin, clotrimazole, econazole, ketoconazole, miconazole and natamycin at 1 mg l(-1), the number of PMNs migrating was significantly reduced. After 3 h of exposure to 10 mg l(-1), not one of the drugs tested had any discernable effect on the viability of the PMNs, or the complement. The anti-inflammatory activity of the drugs is discussed and whilst the chemosuppression of PMN chemotaxis may be an undesirable feature in a drug used to treat systemic mycoses, it is unlikely to have any adverse effect in the therapy of the dermatophytoses.
Rhizopus species was isolated from 8 cases of gastric ulcer in piglets who died 2-5 days after birth. The prevalence of the condition was 0.775% of 1032 live births, and it was the cause of neonatal death in 3.65% of 219 instances. The gross and microscopic pathologies of the lesions are described.
Some aspects pertaining to the ecology of the dimorphic fungus, Paracoccidioides brasiliensis, are reviewed. The available facts concerning the interactions among the only known host (man), the environment (limited to certain Latin-American countries) and the parasite (with an unknown habitat), are analysed. Efforts are made to detect clue circumstances which may lead to discovery of the fungus micro-niche. An analysis of P. brasiliensis mycelial form reveals that such a form has the required capabilities to be the natural infectious form. Its requirements for a moist environment in vitro as well as the high relative humidity predominating in the heart of the endemic areas point towards the possibility of an aquatic--or at least, an extremely humid--habitat for P. brasiliensis.
The effect of the imidazole oxiconazole and the morpholine derivative Ro 14-4767/002 on the sterol metabolism of Candida albicans was investigated at different periods of growth. Ergosterol, representing the main sterol component of control cells, was markedly reduced in oxiconazole-treated and Ro 14-4767/002-treated cells. However, the total sterol content of the cells treated with both drugs was increased due to accumulation of other sterols not present in control cells: in oxiconazole-treated cells 24-methenedihydrolanosterol, 4,14-dimethylfecosterol and 14-methylfecosterol accumulated, indicating an inhibition of C14-demethylation. This is in agreement with the mode of action described for other azoles in various pathogen fungi. In Ro 14-4767/002-treated cells the main sterol accumulated was ignosterol, indicating an inhibition of delta 14-sterol reductase and delta 8-delta 7-isomerase. This inhibition has not been described before in human pathogens although it has been previously found in plant pathogenic fungi treated with fenpropimorph.
Mycotic keratoconjuntivitis caused by Acremonium kiliense in a German Shepherd bitch was diagnosed with the aid of laboratory tests. The dog presented with photophobia, tearing, corneal edema and reduction of the visual capacity. A thick white layer partially covered the right eye. The left eye showed irritation and small brown stains which were diagnosed as pigmentary keratitis. The initial treatment consisted of 2% yellow mercury oxide. Natamycin was used as final treatment. Seven days later, the natural brightness of the eye as well as the visual capacity were restored.
