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At least 19 recordsLinked to original sources

PubMed1978

Pigment production by Cryptococcus neoformans and other Cryptococcus species from aminophenols and diaminobenzenes.

Cryptococcus neoformans and other Cryptococcus species can produce pigment(s) from many aminophenol and diaminobenzene compounds. Pigment production from these compounds is similar to the conversion of diphenols to melanin by C. neoformans. Several pigmentation patterns (resulting in the identification or grouping of Cryptococcus species) have been observed by using diaminobenzene and aminophenol compounds as substrates. The most common pigmentation pattern observed was pigment production by both C. neoformans and C. terreus. In contrast to the diphenols, only two aminophenols (4-hydroxymetanilamide and 3-aminotyrosine) were found to be highly specific as substrates. They allowed only C. neoformans to produce pigment. When 4-aminosalicylic acid was the substrate, a unique pattern was observed because only C. terreus, C. diffluens, and C. albidus produced pigment. Finally, a pattern was observed in which C. neoformans produced large amounts of pigment from aminophenol and diaminobenzene compounds, whereas the other Cryptococcus species produced smaller amounts. A simplified scheme with three substrates resulted in the identification of C. terreus and C. neoformans as well as two groups of other Cryptococcus species, group I (C. albidus and C. diffluens) and group II (C. laurentii and C. luteolus).

Aminobenzoates↗

PubMed1979

Further simplification of the Guizotia abyssinica seed medium for identification of Cryptococcus neoformans and Cryptococcus bacillispora.

A simplified Guizotia abyssinica seed-based medium for presumptive diagnosis of Cryptococcus neoformans and C. bacillispora (Paliwal and Randhawa 1978) was further simplified by replacing seed extract with pulverized seeds. This medium gives unambiguous results, avoids false-positive reactions with 13 other yeastlike organisms, and is simple and relatively inexpensive to prepare.

Cryptococcus↗

PubMed2025

Unisexual reproduction in the global human fungal pathogen Cryptococcus neoformans.

The human fungal pathogen Cryptococcus species complex (encompassing Cryptococcus neoformans, Cryptococcus deneoformans, and the Cryptococcus gattii species complexes) exhibits diversity in sexual reproduction, including α-a mating, pseudosexual reproduction, as well as unisexual reproduction initiated from a single isolate or between isolates of the same mating type. A central conundrum is that while most Cryptococcus natural populations exhibit significant α mating-type bias, genetic and genomic analyses show recombination occurs in nature. The discovery of unisexual reproduction in C. deneoformans provided insight; however, thus far, unisexual reproduction has never been directly observed in the predominant global pathogenic species C. neoformans. Here, we provide evidence that mutating the RIC8 gene, which encodes a conserved guanine nucleotide exchange factor (GEF) involved in both chaperoning and activating Gα proteins, enables unisexual reproduction in C. neoformans. Additionally, we show that genetic variation in the natural population promotes unisexual reproduction, and unisexual reproduction in C. neoformans involves canonical meiotic recombination. Finally, we found that deletion of both GPA2 and GPA3 in the MATα background leads to self-filamentation without sporulation, suggesting that differential modulation of the Gα proteins, likely involving Ric8, could underlie the switch between different modes of sexual reproduction in Cryptococcus. Our study further highlights that the highly conserved Ric8 GEF can act as an important regulator of cellular development in response to environmental stimuli and could modulate sexual reproduction in nature. We hypothesize that unisexual reproduction occurs much more frequently in nature than currently appreciated, and possibly in other fungi and microbial eukaryotes as well.

Cryptococcus neoformans↗

PubMed1978

Pigmentation and autofluorescence of Cryptococcus species after growth on tryptophan and anthranilic acid media.

Cryptococcus neoformans and Candida albicans produced a pink pigment from media containing tryptophan. Approximately 30% of the C. neoformans strains produced large amounts of the pink (purple after 6 days) pigment in the absence of light whereas 70% of the Cryptococcus neoformans strains, as well as C. laurentii, C. albidus, C. diffluens, and C. albicans also produced the pink pigment with light being required for significant early production (2--6 days). Significant production did occur for Cryptococcus but not Candida species in the dark after extended incubation (10--25 days). C. terreus produced brown pigments from tryptophan and C. luteolus produced a trace of a buff pigment. Most Candida species produced either pink or brown pigments but not both. In contrast, many Cryptococcus species producing the pink pigment simultaneously produced brown pigments. C. terreus, C. albidus, and C. diffluens produced brown pigments from anthranilic acid whereas C. neoformans, C. laurentii, C. luteolus, and the medically important Candida species did not produce significant amounts of pigments from anthranilic acid. Cryptococcus and Candida species were autofluorescent when tryptophan was a major nitrogen source whereas yeast cell autofluorescence was not observed when anthranilic acid.

Candida↗

PubMed1978

Hypersensitivity pneumonitis with antibodies to Cryptococcus neoformans.

Clinical and immunological studies were made in forty-two patients diagnosed as suffering from hypersensitivity pneumonitis at Osaka Prefectural Habikino Hospital between 1973 and 1977. All the sera from forty-one patients tested had high titres of antibody against Cryptococcus neoformans in indirect fluorescent antibody tests, and twelve also had precepitins against Cryptococcus neoformans polysaccharide. Only about 10% of control sera from patients with other lung diseases had low titres of antibody against Cryptococcus neoformans. Antibody against Cryptococcus neoformans was also found frequently in the sera of asymptomatic members of the families of the patients. A possible relationship of Cryptococcus neoformans to hypersensitivity pneumonitis is suggested.

Adolescent↗

PubMed1992

Aerosolized liposomal amphotericin B for treatment of pulmonary and systemic Cryptococcus neoformans infections in mice.

Cryptococcus infections of the lung and central nervous system have become major problems in immuno-compromised patients, leading to the need for additional treatment protocols. We have utilized a Cryptococcus-mouse model that mimics human cryptococcal disease to evaluate the efficacy of amphotericin B-liposomes (AmpB-Lip) when delivered by small-particle aerosol (SPA). In the model, initial intranasal inoculation leads to a pulmonary infection that spreads after 2 to 3 weeks to distant organs, including the brain. Aerosols of AmpB-Lip that were generated by a Collison nebulizer had mass median aerodynamic diameters of 1.8 microns and contained 10.3 micrograms of AmpB per liter. When AmpB-Lip SPA was begun at 24 h postinoculation, a single 2-h treatment (0.3 mg of AmpB per kg of body weight) was effective in reducing pulmonary Cryptococcus infection. This regimen was more effective than intravenous administration of AmpB-Lip given for 3 continuous days. This single 2-h exposure to AmpB-Lip also was effective in reducing pulmonary Cryptococcus infection when treatment was delayed for 7 or 14 days. At day 21, when organisms had spread to the brain in all animals, the single 2-h aerosol treatment reduced the number of cryptococci in the brain as well as in the lungs. AmpB-Lip SPA administered once for 2 h on days 7, 14, and 21 also was effective in increasing the duration of survival of infected animals. These results demonstrate that aerosolized AmpB-Lip can be effective in treating both local, pulmonary Cryptococcus disease and systemic disease.

Aerosols↗

PubMed1975

Abnormalities in cell-mediated immunity in patients with Cryptococcus neoformans infection.

Cryptococcin, streptokinase-streptodornase (SK-SD), mumps, and purified protein derivative (PPD) were used for skin testing and, with whole killed Cryptococcus neoformans, were used in migration inhibition and lymphocyte transformation assays of control subjects and patients with past or present disseminated C. neoformans infection. Cryptococcin was found to differentiate control subjects grouped by known Cryptococcus exposure. Cryptococcin and C. neoformans were effective in stimulating leukocyte migration inhibition and lymphocyte transformation in the cryptococcin skin test-positive control subjects. Fifteen apparently normal patients who had been cured of cryptococcosis were found, as a group, to have impaired responsiveness to skin testing with cryptococcin and mumps, minimal leukocyte migration inhibition when stimulated with cryptococcin or C. neoformans, but normal group responses to cryptococcin in Cryptococcus-induced lymphocyte transformation. Six patients with known predisposing conditions to disseminated infection (sarcoid, lymphoma, leukemia, steroid therapy) had markedly diminished responses to most skin tests and in vitro assays. It is suggested that the apparently normal individual who develops disseminated cryptococcal infection has subtle defects in cellular immunity that may have antedated and predisposed to infection.

Antigens, Fungal↗

PubMed1979

Identification of species of Candida, Cryptococcus, and Torulopsis by gas-liquid chromatography.

Gas-liquid chromatography was used to identify species of Candida, Cryptococcus, and Torulopsis by fatty-acid analysis of the whole-cell hydrolysate. Candida albicans characteristically revealed 2-OH C14:0 and C19:0 (chain length:number of double bonds); these were absent in other organisms. Candida curvata was characterized by a ratio of C16:1 to C16:0 of greater than 1.0. Candida guilliermondii contained C10:0, and Candida tropicalis had no C12:0, these features were used for their identification. Cryptococcus was characterized by the absence of C16:1. Torulopsis was characterized by a C16:1 to C16:0 ratio of greater than 10 accompanied by the presence of one unidentified fatty acid. These data suggested that certain Candida, Cryptococcus, and Torulopsis (the clinically important yeast-like organisms) may be identified by gas-liquid chromatography.

Candida↗

PubMed1977

Diagnostic medium containing inositol, urea, and caffeic acid for selective growth of Cryptococcus neoformans.

An agar medium containing inositol and urea as sole carbon and nitrogen sources, caffeic acid and ferric citrate as agents for the selective pigmentation of Cryptococcus neoformans, gentamicin as a broad-spectrum bacterial antibiotic, and yeast nitrogen base without amino acids and ammonium sulfate (Difco) was tested against 137 clinical isolates, 4 survey specimens, and 11 ATCC yeast and yeast-like strains. All 28 strains of C. neoformans showed heavy growth and dark brown pigmentation after 36 h. All other tested species of Cryptococcus showed heavy growth after 36 h but only light brown pigmentation after 48 h. No growth was observed in any tested strains of Geotrichum, Pityrosporum, Rhodotorula, Saccharomyces, and Torulopsis. Only the Cryptococcus-like Candida humicola grew of the 8 species and 62 strains of Candida tested. Six of 15 strains of Trichosporon cutaneum and 1 of 2 strains of Trichosporon pullulans showed moderate growth after 48 h. Very different colonial and microscopic morphology and/or the absence of brown pigmentation easily differentiated these strains of T. cutaneum, T. pullulans, and C. humicola from C. neoformans. The growth- and pigmentation-providing characteristics of the medium were unaffected by 2 h of exposure to 254 nm of ultraviolet light.

Agar↗

PubMed1992

In vitro responses of cheetah mononuclear cells to feline herpesvirus-1 and Cryptococcus neoformans.

In vitro T cell function by domestic cats and cheetahs to two common pathogens, feline herpesvirus-1 (FHV-1) and Cryptococcus neoformans, was assessed. Peripheral blood mononuclear cells (PBM) were stimulated with two strains of UV-inactivated FHV-1, whole heat-killed organisms or capsular antigen of Cryptococcus neoformans, and proliferative responses measured. As a group, cheetah PBM responded significantly poorer than domestic cat PBM when cultured with FHV-1. However, individual cheetah responses varied widely. Supplementation of cultures with exogenous interleukin 2 (IL-2) significantly increased the level of response of individual cheetahs to both strains of FHV-1. Cheetah sera contained slightly higher neutralizing antibody titers to FHV-1 than did domestic cat sera, suggesting that B cells function adequately in cheetahs. When stimulated with Cryptococcus neoformans, both species had similar incidences of positive proliferative responses. These data demonstrate that cheetahs exhibit heterogeneous responses to specific antigens, similar to domestic cats. However, a lower group response to FHV-1 in cheetahs suggests species differences occur. In addition, level of variability in major histocompatibility complex (MHC) class I-like genes, as determined by Southern blot hybridization, does not appear to correlate with a uniform response in in vitro functional assays. Therefore, additional mechanisms influence the final outcome of the immune response.

Acinonyx↗

PubMed2025

The complex evolution and genomic dynamics of mating-type loci in Cryptococcus and Kwoniella.

Sexual reproduction in basidiomycete fungi is governed by MAT loci (P/R and HD), which exhibit remarkable evolutionary plasticity, characterized by expansions, rearrangements, and gene losses often associated with mating system transitions. The sister genera Cryptococcus and Kwoniella provide a powerful framework for studying MAT loci evolution owing to their diverse reproductive strategies and distinct architectures, spanning bipolar and tetrapolar systems with either linked or unlinked MAT loci. Building on recent comparative genomic analyses, we generated additional chromosome-level assemblies, uncovering distinct trajectories shaping MAT loci organization. Contrasting with the small-scale expansions and gene acquisitions observed in Kwoniella, our analyses revealed independent expansions of the P/R locus in tetrapolar Cryptococcus, possibly driven by pheromone gene duplications. Notably, these expansions coincided with a pronounced GC-content reduction best explained by reduced GC-biased gene conversion following recombination suppression, rather than relaxed codon usage selection. Diverse modes of MAT locus linkage were also identified, including three previously unrecognized transitions: one resulting in a pseudobipolar arrangement and two leading to bipolarity. All three transitions involved translocations. In the pseudobipolar configuration, the P/R and HD loci remained on the same chromosome but genetically unlinked, whereas the bipolar transitions additionally featured rearrangements that fused the two loci into a nonrecombining region. Mating assays confirmed a sexual cycle in Cryptococcus decagattii, demonstrating its ability to undergo mating and sporulation. Progeny analysis in Kwoniella mangrovensis revealed substantial ploidy variation and aneuploidy, likely stemming from haploid-diploid mating, yet evidence of recombination and loss of heterozygosity indicates that meiotic exchange occurs despite irregular chromosome segregation. Our findings underscore the importance of continued diversity sampling and provide further evidence for convergent evolution of fused MAT loci in basidiomycetes, offering new insights into the genetic and chromosomal changes driving reproductive transitions.

Genes, Mating Type, Fungal↗

PubMed1976

[Relations within genus Cryptococcus (Sanfelice) Vuillemin].

A collection of 49 Cryptococcus strains was studied by means of 62 tests, which emphasized morphological, physiological and biochemical properties. The experimental results were subjected to computer analysis using matching coefficient and taxanomic distance. Cluster analysis were carried out using average linkage method. Two clusters and one individual strain were formed, the first cluster represented the genus Cryptococcus, the second cluster and the individual strain did not belong to this genus. The cluster of the genus Cryptococcus was divided into five phenons: Laurentii Neoformans, Albidus, Terreus and Aerius. The belonging of strains to these phenons is discussed comparing the results with those of GC% content in DNA, of the production of coenzyme Q and many other. The quick identification phenons was suggested.

Alcohols↗

PubMed2025

Unisexual reproduction in the global human fungal pathogen Cryptococcus neoformans.

The human fungal pathogen Cryptococcus species complex (encompassing C. neoformans, C. deneoformans, and the C. gattii species complexes) exhibit diversity in sexual reproduction, including α-a mating, pseudosexual reproduction, as well as unisexual reproduction initiated from a single isolate or between isolates of the same mating type. A central conundrum is that while most Cryptococcus natural populations exhibit significant α mating-type bias, genetic and genomic analyses show recombination occurs in nature. The discovery of unisexual reproduction in C. deneoformans provided insight; however, thus far unisexual reproduction has never been directly observed in the predominant global pathogenic species C. neoformans. Here, we provide evidence that mutating the RIC8 gene, which encodes a conserved guanine nucleotide exchange factor (GEF) involved in both chaperoning and activating Gα proteins, enables unisexual reproduction in C. neoformans. Additionally, we show that genetic variation in the natural population promotes unisexual reproduction, and unisexual reproduction in C. neoformans involves canonical meiotic recombination. Finally, we found that deletion of both GPA2 and GPA3 in the MATα background leads to self-filamentation without sporulation, suggesting that differential modulation of the Gα proteins, likely involving Ric8, could underlie the switch between different modes of sexual reproduction in Cryptococcus. Our study further highlights that the highly conserved Ric8 GEF can act as an important regulator of cellular development in response to environmental stimuli and could modulate sexual reproduction in nature. We hypothesize that unisexual reproduction occurs much more frequently in nature than currently appreciated, and possibly in other fungi and microbial eukaryotes as well.

G protein↗

PubMed1978

An ultrastructural examination of the interaction between macrophages and Cryptococcus neoformans.

The interaction of mononuclear phagocytes with Cryptococcus neoformans was examined in vitro and in vivo using ultrastructural techniques. Immune serum roughens the surface of the yeast and in the first 2 hr, increases the number of organisms attaching to the macrophage surface, as well as the number of contacts between individual yeasts and the phagocyte. Contact is established by means of thin filopodia and cytoplasmic flaps. During the next few days the macrophages increase in size, and, by intimate apposition of their contiguous cell surfaces, a cellular barrier surrounds the now enclosed yeast. These events are accompanied by thinning of fungal capsule, degradation of the enclosed cryptococcus, and the formation of macrophage polykaryons. Electron cytochemical techniques for peroxidase reveal that these multinucleated cells are formed predominantly by the fusion of stimulated macrophages. Destruction of the enclosed yeast probably results from the secretion of various agents by the surrounding cells.

Animals↗

PubMed1978

Epidemiology of Cryptococcus neoformans.

The concept of the epidemiology of Cryptococcus neoformans as the causative agent of cryptococcosis and as a basidiomycetous yeast is based on the fact that bird manure has been until now its only known habitat but not plant material which likewise harbours various nonpathogenic Cryptococcus species. It could be shown that the possible influence of nutritional factors on the morphology and morphogenesis earns attention not only in view of the epidemiology of C. neoformans but of its perfect states, too.

Animals↗

PubMed1979

Survey of Cryptococcus neoformans in the respiratory tract of patients with bronchopulmonary disorders and in the air.

Cryptococcus neoformans was cultured from 9 (1%) of 835 clinical specimens examined from the respiratory tract of patients. These isolations came from 3 (0.4%) of the760 patients; 8 isolates were from sputum and one from urine. The fungus was not demonstrable in the air at a selected site during a 2-year study although other species of Cryptococcus, namely, C. albidus, C. ater, C. flavus, C. laurentii, C. magnus, C. terreus and C. uniguttulatus were isolated. The three C. neoformans positive patients were males, with pulmonary tuberculosis as the primary disease and history of repeated exposure to pigeon excreta in two. None of these patients manifested any overt signs and symptoms specificially attributable to cryptococcosis, nor did they receive any antifungal therapy. Repeated isolations of C. neoformans from sputum, a positive urine culture and demonstration of cryptococcal antibodies in a serum specimen, followed by negative cultures and serology, suggested that patient 1 had spontaneously recovered from an episode of benign, minimal pulmonary cryptococcosis. Patients 2 and 3 probably carried the fungus as a transient resident of the respiratory tract. The results suggest that C. neoformans is of uncommon occurrence in the respiratory tract of patients with bronchopulmonary disorders and that the isolation of the fungus from this site may not necessarily imply an etiologic relationship.

Adult↗

PubMed1975

Combined activity of amphotericin B and 5-fluorocytosine against Cryptococcus neoformans in vitro and in vivo in mice.

The in vitro and in vivo activities of amphotericin B and 5-fluorocytosine (5-FC) alone and in combination were studied to determine possible drug interactions against two strains of Cryptococcus neoformans, one sensitive to 5-FC and one resistant to 5-FC. In vitro tube dilution studies demonstrated only additive effects with the 5-FC-sensitive organism but antagonism with eth 5-FC-resistant organism. A mouse model of cryptococcal meningitis allowed comparative drug trails in a new model for the detection of drug interactions. Drug combinations were no more effective against meningitis caused by the 5-FC-sensitive organism than the additive effects of the individual drugs. However, meningitis caused by the 5-FC-resistant Cryptococcus responded less to drug combinations than to either drug alone. Serum levels of amphotericin B and 5-FC were comparable in all groups. No evidence of toxicity from the drug combinations was found. No inhibition of development of resistance to 5-FC by the combination with amphotericin B was detected.

Amphotericin B↗

PubMed1975

Pigment production by Cryptococcus neoformans from para- and ortho-Diphenols: effect of the nitrogen source.

Cryptococcus neoformans produced pigments when p-diphenols were substrates in a glucose-amino acid-salts medium. The best substrates were 2.5-dihydroxybenzoic acid and 2,5-dihydroxybenzenesulfonic acid. In contrast to the cellular pigment production from o-diphenols (hydroxyl groups in the 2,3- or 3,4-position of phenyl ring), the p-diphenols (1,4- or 2,5-positions for the hydroxyl groups) produced large amounts of soluble pigments that diffused into the medium. When an optimal source of nitrogen (glutamine, glycine, and asparagine) was used, 89% of the C. neoformans strains produced pigments from p-diphenols. In contrast, 0 to 67% of the strains produced pigments when a suboptimal nitrogen source (proline, ammonium sulfate, ornithine, and methionine) was used. When glutamine-glycine-asparagine was the nitrogen source, 100% of the C. neoformans strains produced pigments from o0diphenols, whereas 77 to 100% of the strains produced pigment when proline-ammonium sulfate-ornithine-methionine was the nitrogen source. Cryptococcus species other than C. neoformans and all tested Candida species failed to produce pigments from any of the substrates except when hydroquinone was used. A combination of glutamine-glycine-asparagine and 3,4-dihydroxyphenylalanine allowed differentiation of colonies of C. neoformans from C. albicans in 3 to 6 days. These data showed that pigment production from o- and p-diphenols served as an excellent biochemical test for the identification of C. neoformans.

Asparagine↗