Evidence for the Role of Calcineurin in Morphogenesis and Calcium Homeostasis during Mycelium-to-Yeast Dimorphism of
            <i>Paracoccidioides brasiliensis</i>

Campos, Cláudia Barbosa Ladeira de; Benedette, Joao Paulo T. Di; Morais, Flavia Villaça; Ovalle, Rafael; Nóbrega, Marina P.

doi:10.1128/ec.00110-08

Cited by 40 publications

(24 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Calcineurin is known to regulate pathogenesis and morphogenesis in a temperature-dependent fashion in C. albicans, Cryptococcus neoformans, and Paracoccidioides brasiliensis (17)(18)(19)(20)(21). We found that the calcineurin inhibitor tacrolimus had a profound fungicidal and proapoptotic activity against Mucorales at a high temperature compared to azoles alone.…”

Section: Discussionmentioning

confidence: 70%

See 1 more Smart Citation

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Shirazi

Pontikos

Walsh

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The high mortality rate of mucormycosis with currently available monotherapy has created interest in studying novel strategies for antifungal agents. With the exception of amphotericin B (AMB), the triazoles (posaconazole [PCZ] and itraconazole [ICZ]) are fungistatic in vitro against Rhizopus oryzae. We hypothesized that growth at a high temperature (42°C) results in fungicidal activity of PCZ and ICZ that is mediated through apoptosis. R. oryzae had high MIC values for PCZ and ICZ (16 to 64 g/ml) at 25°C; in contrast, the MICs for PCZ and ICZ were significantly lower at 37°C (8 to 16 g/ml) and 42°C (0.25 to 1 g/ml). Furthermore, PCZ and ICZ dose-dependent inhibition of germination was more pronounced at 42°C than at 37°C. In addition, intracellular reactive oxygen species (ROS) increased significantly when fungi were exposed to antifungals at 42°C. Characteristic cellular changes of apoptosis in R. oryzae were induced by the accumulation of intracellular reactive oxygen species. Cells treated with PCZ or ICZ in combination with hyperthermia (42°C) exhibited characteristic markers of early apoptosis: phosphatidylserine externalization visualized by annexin V staining, membrane depolarization visualized by bis-[1,3-dibutylbarbituric acid] trimethine oxonol (DiBAC) staining, and increased metacaspase activity. Moreover, terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling (TUNEL) assay and DAPI (4=,6-diamidino-2-phenylindole) staining demonstrated DNA fragmentation and condensation, respectively. The addition of N-acetylcysteine increased fungal survival, prevented apoptosis, reduced ROS accumulation, and decreased metacaspase activation. We concluded that hyperthermia, either alone or in the presence of PCZ or ICZ, induces apoptosis in R. oryzae. Local thermal delivery could be a therapeutically useful adjunct strategy for these refractory infections.

show abstract

Section: Discussionmentioning

confidence: 70%

“…Specifically, in pathogenic fungi, the calcineurin pathway functions as an important "circuit" for fungal homeostatic cell responses, which counteracts the toxic effects of antifungals in the cell membrane and cell wall, thus contributing to antifungal resistance (19)(20)(21).…”

mentioning

confidence: 99%

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Shirazi

Pontikos

Walsh

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…A filamentous culture grown at 28°C for 24 h, if transferred to higher temperature or kept at 4°C, an intermediate form along with yeast type was found to form at the bottom of the culture broth, keeping the surface filaments apparently unchanged. The dimorphic transition from mycelium to yeast (M-Y) was triggered by a temperature shift from 25 to 37°C and was critical for pathogenicity [23,24]. In the present strain, room temperature (28-30°C) provided a condition for mycelial development, while increased temperature (37°C and above) brought about a prompt shift from mycelial-yeast form, probably due to some altered programme of gene expression.…”

Section: Effect Of Temperaturementioning

confidence: 70%

Effect of Extracellular Factors on Growth and Dimorphism of Rhizopus oryzae with Multiple Enzyme Synthesizing Ability

2011

View full text Add to dashboard Cite

Rhizopus oryzae PR7 MTCC 9642 was a dimorphic fungus that showed a regular 90 days cycle of filament (mycelium) to pellet (yeast) transformation through a distinct bottom dwelling intermediate state and the pellets never revert back to filamentous form. Apart from the normal cycle, high temperature (37°C and above) and extreme pH also induced the yeast formation. Among the ions tested, calcium and chloride ions were found to restore the filamentous morphology, even in extreme pH and temperature. Cysteine HCl also played noteworthy role in maintaining mycelial growth even at adverse condition. Immobilized spores showed the appearance of intermediate form instead of typical yeast form even at high temperature. The strain could produce a number of extracellular hydrolytic enzymes like cellulolytic, xylanolytic, pectinolytic and amylolytic enzymes. The pellet and mycelial forms were found to be a better producer of cellulaselignocellulase enzymes and amylolytic enzymes respectively, which might be correlated with their infectivity. Increase in inoculum size, agitation during cultivation, change in carbon and nitrogen source failed to induce mycelial growth in extreme conditions, which might be explained as irreversible change of configuration of protein responsible for mycelial development.

show abstract

“…15 The signaling by calcium is very important for fungal virulence and drug resistance. 1,2 Calcineurin has been demonstrated to be required for virulence in human fungal pathogens, such as Cryptococcus spp, Candida spp, Paracoccidioides brasiliensis, and Aspergillus fumigatus; [16][17][18][19][20][21][22][23] and fungal plant pathogens, such as Sclerotinia scleotiorum, Botrytis cinerea, Magnaporthe oryza, and Ustilago spp. [24][25][26][27][28] In all these fungal pathogens, calcineurin is important for growth, morphology, state transitions, cation homeostasis, stress responses, and cell membrane and cell wall integrity pathways.…”

Section: Introductionmentioning

confidence: 99%

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

et al. 2016

View full text Add to dashboard Cite

Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. The signaling by calcium is very important for A. fumigatus pathogenicity and it is regulated by the transcription factor CrzA. We have previously used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, the putative flavin transporter, flcA. This transporter belongs to a small protein family composed of FlcA, B, and C. The DflcA null mutant showed several phenotypes, such as morphological defects, increased sensitivity to calcium chelating-agent ethylene glycol tetraacetic acid (EGTA), cell wall or oxidative damaging agents and metals, representative of deficiencies in calcium signaling and iron homeostasis. Increasing calcium concentrations improved significantly the DflcA growth and conidiation, indicating that DflcA mutant has calcium insufficiency. Finally, DflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) and were avirulent in a low dose murine infection model.

show abstract

Evidence for the Role of Calcineurin in Morphogenesis and Calcium Homeostasis during Mycelium-to-Yeast Dimorphism of Paracoccidioides brasiliensis

Cited by 40 publications

References 38 publications

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Hyperthermia Sensitizes Rhizopus oryzae to Posaconazole and Itraconazole Action through Apoptosis

Effect of Extracellular Factors on Growth and Dimorphism of Rhizopus oryzae with Multiple Enzyme Synthesizing Ability

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

Contact Info

Product

Resources

About