Nutritional studies on<i>Paracoccidioides brasiliensis</i>: the role of organic sulfur in dimorphism

Paris, Sophie; Duran-Gonzalez, Silvia; Mariat, F.

doi:10.1080/00362178585380151

Cited by 39 publications

(32 citation statements)

References 16 publications

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“…This mutant is completely virulent, which excludes inorganic S compounds (except H 2 S) and taurine as being required S sources in vivo. This result correlates with previously reported information on the pathogenic fungus Paracoccidioides brasiliensis: this fungus also penetrates the human body through the respiratory tract to infect lung alveoli, and it is known that the yeast form, the parasitic morphotype, cannot assimilate inorganic S sources (86)(87)(88) and, thus, must feed on organic S compounds. Interestingly, the sF⌬ strain was furthermore unable to grow on BSA as a source of sulfur and/or nitrogen.…”

Section: Discussionsupporting

confidence: 81%

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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e Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. Here, we have investigated sulfur (S) utilization by the human-pathogenic mold Aspergillus fumigatus during invasive growth. Our data reveal that inorganic S compounds or taurine is unlikely to serve as an S source during invasive pulmonary aspergillosis since a sulfate transporter mutant strain and a sulfite reductase mutant strain are fully virulent. In contrast, the S-containing amino acid cysteine is limiting for fungal growth, as proven by the reduced virulence of a cysteine auxotroph. Moreover, phenotypic characterization of this strain further revealed the robustness of the subordinate glutathione redox system. Interestingly, we demonstrate that methionine synthase is essential for A. fumigatus virulence, defining the biosynthetic route of this proteinogenic amino acid as a potential antifungal target. In conclusion, we provide novel insights into the nutritional requirements of A. fumigatus during pathogenesis, a prerequisite to understanding and fighting infection.

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Section: Discussionsupporting

confidence: 81%

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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“…The observations of Paris et al [26] that yeast cells of P. brasiliensis were unable to grow in the presence of inorganic sulphur, were confirmed by the array experiments in which the genes coding sulphur metabolism enzymes such as atp sulphurylase, aps kinase, paps redutase and choline sulphatase showed to be up-regulated in yeast cells of this pathogen, indicating the auxotrophic status for cysteine of the pathogenic phase of this fungus [23,24,27].…”

Section: Introductionsupporting

confidence: 63%

“…brasiliensis has been shown to be refractory to classical genetic analysis. Recently, however, careful analyses have established that it has a genome of [26][27][28][29][30][31][32][33][34][35] Mb distributed in four or five chromosomes [3][4][5]. Ploidy is not consensual; some groups have proposed several isolates to be diploid [3,4], whereas other have used different techniques to propose that most isolates be either haploid or aneuploid [5].…”

Section: Introductionmentioning

confidence: 99%

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

et al. 2008

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Paracoccidioiddes brasiliensis is a thermodimorphic fungus endemic to Latin America, where it causes the most prevalent systemic mycosis, paracoccidioidomycosis (PCM). DNA microarray technology has been used to identify patterns of gene expression when a microbe is confronted with conditions of interest, such as in vitro and/or ex vivo interaction with specific cells. P. brasiliensis is one organism that has benefited from this approach. Even though its genome has not been sequenced yet, much has been discovered from its transcriptome and DNA array analyses. In this review, we will outline the current knowledge in P. brasiliensis transcriptome, with focus on differential expression analysis in vitro and on the discussion of the genes that are controlled during the host-pathogen interaction ex vivo in order to give insights into the pathobiology of this fungus. In vitro experiments enabled the delineation of whole metabolic pathways; the description of differential metabolism between mycelium and yeast cells and of the mainly signaling pathways controlling dimorphism, high temperature growth, thermal and oxidative stress, and virulence/ pathogenicity. Recent ex vivo experiments provided advances on the comprehension of the plasticity of response and indicate that P. brasiliensis is not only able to undergo fast and dramatic expression profile changes but can also discern subtle differences, such as whether it is being attacked by a macrophage or submitted to the bloodstream route conditions.

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“…As shown by Paris et al (223), the mycelial phase of the fungus appears to be prototrophic: nine isolates of the fungus were studied and found capable of growth at 23°C in the absence of essential amino acids. On the other hand, in their yeast phase the same isolates were shown to require an accessory growth factor for development, a sulfur-containing amino acid (223).…”

Section: Etiologic Agentmentioning

confidence: 99%

Paracoccidioidomycosis: an update

1993

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This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.

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Nutritional studies onParacoccidioides brasiliensis: the role of organic sulfur in dimorphism

Cited by 39 publications

References 16 publications

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

Paracoccidioidomycosis: an update

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