Mycelial- to yeast-phase transitions of the dimorphic fungi Blastomyces dermatitidis and Paracoccidioides brasiliensis

Abstract

The physiological changes that occur during the mycelial-to yeast-phase transitions induced by a temperature shift from 25 to 37°C of cultures of Blastomyces dermatitidis and Paracoccidioides brasiliensis can be divided into three stages. The triggering event is a heat-related insult induced by the temperature shift which results in partial uncoupling of oxidative phosphorylation and declines in cellular ATP levels, respiration rates, and concentrations of electron transport components (stage 1). The cells then enter a stage in which spontaneous respiration ceases (stage 2), and finally, there is a shift into a recovery phase during Which transformation to yeast morphology occurs (stage 3). Cysteine is required during stage 2 for the operation of shunt pathways which permit electron transport to bypass blocked portions of the cytochrome system. The mycelial-to yeast-phase transitions of these two fungi are very similar to that of Histoplasma capsulatum. Therefore, these three dimorphic fungal pathogens have evolved parallel mechanisms to adjust to the temperature shifts which induce these mycelial-to yeast-phase transitions.Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum are dimorphic pathogenic fungi. Although there are some differences in geographic distribution and clinical presentation of disease caused by these fungi, they all can cause systemic infections in humans. Other similarities include the existence as mycelia in nature and yeast in infected tissue, growth as mycelia in cultures incubated at 25°C and as yeast at 370C, and induction of reversible phase transitions by switching between 25 and 37°C (7).In previous studies (5, 5a, 8) we characterized the mycelial-to yeast-phase transition of H. capsulatum induced by the temperature shift from 25 to 37°C and also by shifts to temperatures as high as 43°C. We found that the physiological changes that occur in this fungus when the temperature is raised can be divided into three distinct stages. Stage 1, which immediately follows the temperature shift, is characterized by partial or complete uncoupling of oxidative phosphorylation, an immediate decline in ATP levels, and a progressive decrease in respiration rates over 24 h. After 24 to 40 h, the cells enter stage 2, a dormant period of 4 to 6 days that is characterized by absent or low rates of respiration, decreased concentrations of mitochondrial electron transport components, and inhibition of RNA and protein synthesis. Stage 3 is characterized by increasing concentrations of cytochrome components, resumption of normal respiration, and completion of the transition to yeast morphology.The severity of the changes during the transition depends on the thermal tolerance of the strain of H. capsulatum and the level of the temperature of incubation (7). When the temperature elevation is high enough, spontaneous respiration ceases in stage 2, and cysteine or other sulfhydrylcontaining compounds are required for the operation of shunt pathways which permit electron transport t...

cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis.

“…Biochemical evidence for a role for cAMP in morphogenesis has been described for a number of different pathogenic and saprophytic fungi, including many dimorphic species (Maresca et al 1977;Medoff et al 1981Medoff et al , 1987Paris and Garrison 1983;Brunton and Gadd 1989). For example, an increase in intracellular cAMP has been reported during germ-tube formation and subsequent hy-Cold Spring Harbor Laboratory Press on April 4, 2019 -Published by genesdev.cshlp.org Downloaded from phal growth in the dimorphic pathogens H. capsulatum (Maresca et al 1977;Medoff et al 1981), C. albicans (Niimi et al 1980;Sabie and Gadd 1992), and Blastomyces dermatitidis (Paris and Garrison 1983).…”

Infections in Patients with Inherited Defects in Phagocytic Function

“…Infection begins with aspiration of conidia and uptake by neutrophils and macrophages via CD11/CD18 receptors. The conidia transform to yeast forms, which proliferate in macrophages (180,200). T cells and macrophages provide active defense, and neutrophil antimicrobial peptides can inhibit the yeast forms.…”

Molecular and genetic analysis of the Cryptococcus neoformans MET3 gene and a met3 mutant a aThe GenBank accession numbers for the sequences reported in this paper are AY035556 and AF489498.

“…titidis and Paracoccidioides brasiliensis (Medoff et al, 1987). In addition, the methionine\cysteine biosynthetic pathway is of interest from the perspective of antifungal drug development.…”