scholarly journals Mechanism of Growth Regulation of Yeast Involving Hydrogen Sulfide From S-Propargyl-Cysteine Catalyzed by Cystathionine-γ-Lyase

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongkai Gu ◽  
Yufan Sun ◽  
Feizhen Wu

Pathogenic fungi are recognized as a progressive threat to humans, particularly those with the immunocompromised condition. The growth of fungi is controlled by several factors, one of which is signaling molecules, such as hydrogen sulfide (H2S), which was traditionally regarded as a toxic gas without physiological function. However, recent studies have revealed that H2S is produced enzymatically and endogenously in several species, where it serves as a gaseous signaling molecule performing a variety of critical biological functions. However, the influence of this endogenous H2S on the biological activities occurring within the pathogenic fungi, such as transcriptomic and phenotypic alternations, has not been elucidated so far. Therefore, the present study was aimed to decipher this concern by utilizing S-propargyl-cysteine (SPRC) as a novel and stable donor of H2S and Saccharomyces cerevisiae as a fungal model. The results revealed that the yeast could produce H2S by catabolizing SPRC, which facilitated the growth of the yeast cells. This implies that the additional intracellularly generated H2S is generated primarily from the enhanced sulfur-amino-acid-biosynthesis pathways and serves to increase the growth rate of the yeast, and presumably the growth of the other fungi as well. In addition, by deciphering the implicated pathways and analyzing the in vitro enzymatic activities, cystathionine-γ-lyase (CYS3) was identified as the enzyme responsible for catabolizing SPRC into H2S in the yeast, which suggested that cystathionine-γ-lyase might play a significant role in the regulation of H2S-related transcriptomic and phenotypic alterations occurring in yeast. These findings provide important information regarding the mechanism underlying the influence of the gaseous signaling molecules such as H2S on fungal growth. In addition, the findings provide a better insight to the in vivo metabolism of H2S-related drugs, which would be useful for the future development of anti-fungal drugs.

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2636 ◽  
Author(s):  
Laurine Garros ◽  
Samantha Drouet ◽  
Cyrielle Corbin ◽  
Cédric Decourtil ◽  
Thibaud Fidel ◽  
...  

Flaxseeds are a functional food representing, by far, the richest natural grain source of lignans, and accumulate substantial amounts of other health beneficial phenolic compounds (i.e., flavonols, hydroxycinnamic acids). This specific accumulation pattern is related to their numerous beneficial effects on human health. However, to date, little data is available concerning the relative impact of genetic and geographic parameters on the phytochemical yield and composition. Here, the major influence of the cultivar over geographic parameters on the flaxseed phytochemical accumulation yield and composition is evidenced. The importance of genetic parameters on the lignan accumulation was further confirmed by gene expression analysis monitored by RT-qPCR. The corresponding antioxidant activity of these flaxseed extracts was evaluated, both in vitro, using ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and iron chelating assays, as well as in vivo, by monitoring the impact of UV-induced oxidative stress on the lipid membrane peroxidation of yeast cells. Our results, both the in vitro and in vivo studies, confirm that flaxseed extracts are an effective protector against oxidative stress. The results point out that secoisolariciresinol diglucoside, caffeic acid glucoside, and p-coumaric acid glucoside are the main contributors to the antioxidant capacity. Considering the health benefits of these compounds, the present study demonstrates that the flaxseed cultivar type could greatly influence the phytochemical intakes and, therefore, the associated biological activities. We recommend that this crucial parameter be considered in epidemiological studies dealing with flaxseeds.


2019 ◽  
Author(s):  
Wanzhen Su ◽  
Jialin Liu ◽  
Peng Bai ◽  
Baocang Ma ◽  
Wei Liu

Abstract Background Since animals frequently encounter a variety of harmful fungi in nature, their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted the significant involvement of indigenous microbial communities in human health. However, the daunting diversity of mammalian microbiota and host genetic complexity are major obstacles to our understanding of these intricate links between microbiota components, host immune genotype, and disease phenotype. In this study, we sought to develop a bacterium-fungus-Drosophila model to systematically evaluate the anti-fungal effects of commensal bacteria. Results We isolated the pathogenic fungal strain, Diaporthe FY, which was detrimental to the survival and development of Drosophila upon infection. Using Drosophila as a model system, Drosophila-associated Lactobacillus plantarum functioned as a probiotic, and protected the flies from mortality induced by Diaporthe FY. Our results show that L. plantarum hindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, consequently mitigating the toxicity of Diaporthe FY to the hosts. Additionally, the presence of L. plantarum overrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions Diaporthe FY was identified as a potential Drosophila pathogen. Commensal L. plantarum mitigated the susceptibility of Drosophila to pathogenic fungi, providing insight into the natural interplay between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis.


2018 ◽  
Vol 9 (2) ◽  
pp. 219-230 ◽  
Author(s):  
E. Gabrielli ◽  
E. Pericolini ◽  
N. Ballet ◽  
E. Roselletti ◽  
S. Sabbatini ◽  
...  

Previously we demonstrated that the treatment with live Saccharomyces cerevisiae exerts beneficial therapeutic effects against vaginal candidiasis. Here, we address potential mechanisms particularly examining the probiotic capacity to modulate both fungus and host-related factors. We show that the S. cerevisiae-based probiotic markedly affects the expression of virulence traits of Candida albicans such as aspartyl proteinases (SAPs) as well as hyphae-associated proteins Hwp1 and Ece1 in the vaginal cavity. On the host side, the probiotic suppression of the influx of neutrophils caused by the fungus into the vaginas of the mice is likely related to: (1) lower production of interleukin-8; and (2) inhibition of SAPs expression. However, these neutrophils displayed reactive oxygen species hyperproduction and increased killing activity as compared to the neutrophils of placebo-treated mice. There was no evidence of any cytotoxic effect by the probiotic, either when used in vivo on vaginal epithelial cell and organ architecture, or in in vitro in human vaginal epithelium. Inactivated yeast cells did not affect any of the factors above. In summary, the data suggest that the beneficial effect exerted by this S. cerevisiae-based probiotic is the result of its interference with the expression of fungus virulence factors coupled with the modulation of the inflammatory response of the host.


2019 ◽  
Author(s):  
Wei Liu ◽  
Wanzhen Su ◽  
Jialin Liu ◽  
Peng Bai ◽  
Baocang Ma

Abstract Background Animals frequently encounter a variety of harmful fungi in the wild, but their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted significant involvement of indigenous microbial communities in host health, but the daunting complexity of microflora has hampered our understanding of the intricate relationships among them. In this work, we sought to develop a bacterium-fungus-Drosophila model that offered a model to systematically evaluate the anti-fungal effects of commensal bacteria. Results We isolated a pathogenic fungal strain, Diaporthe FY, that was detrimental to the survival and development of Drosophila upon infection. Using Drosophila as a model system, Drosophila-associated Lactobacillus plantarum functioned as a probiotics, and protected flies from mortality induced by Diaporthe FY. Our results shown that L. plantarum hindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, therefore consequently mitigating the toxicity of Diaporthe FY to hosts. In addition, L. plantarum overrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions Diaporthe FY was identified as a potential pathogen to Drosophila. Commensal L. plantarum mitigated the pathogenic fungi-induced susceptibility in Drosophila, providing an insight into the natural interplays between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis.


Author(s):  
Shagufta Habib ◽  
Pawan Gupta ◽  
Sana Shafi Bhat ◽  
Jeena Gupta

Abstract. Citral, one of the main components of lemongrass oil (65–85%), is known to possess various medicinal properties like enhancing skin health and vision-improvement. It also acts as flavoring agent, used in perfumes and skin care products. The objective of this work was to elucidate the biological properties of citral at molecular level using an integrated in silico, in vitro and in vivo approaches. To elucidate this in silico molecular docking studies were performed with in vitro validation by DPPH scavenging activity, MTT assays, enzymatic assays and Chorio Allantoic Membrane (CAM) assay. The in silico analysis demonstrated the potential binding of citral with PPARγ ligand binding domain and vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2). Citral is already a proven anti-oxidant which is further confirmed by increased DPPH inhibition with increased citral concentration (IC50: 6.9 ± 1.68 μg/ml, p < 0.05). The results demonstrated that citral protect yeast cells from cytotoxic effects of hydrogen peroxide and also increase the activities of antioxidant enzymes like GST, SOD and LPO. It was also demonstrated to be cytotoxic to cancerous HeLa cells (IC50: 3.9 ± 0.38 μM, p < 0.01) and was found anti-angiogenic by CAM assay. This study highlights many important pharmaceutical properties of citral which can be explored further to increase its industrial applications.


2006 ◽  
Vol 5 (2) ◽  
pp. 379-390 ◽  
Author(s):  
Wagner L. Batista ◽  
Alisson L. Matsuo ◽  
Luciane Ganiko ◽  
Tânia F. Barros ◽  
Thiago R. Veiga ◽  
...  

ABSTRACT J-domain (DnaJ) proteins, of the Hsp40 family, are essential cofactors of their cognate Hsp70 chaperones, besides acting as independent chaperones. In the present study, we have demonstrated the presence of Mdj1, a mitochondrial DnaJ member, not only in the mitochondria, where it is apparently sorted, but also in the cell wall of Paracoccidioides brasiliensis, a thermodimorphic pathogenic fungus. The molecule (PbMdj1) was localized to fungal yeast cells using both confocal and electron microscopy and also flow cytometry. The anti-recombinant PbMdj1 antibodies used in the reactions specifically recognized a single 55-kDa mitochondrial and cell wall (alkaline β-mercaptoethanol extract) component, compatible with the predicted size of the protein devoid of its matrix peptide-targeting signal. Labeling was abundant throughout the cell wall and especially in the budding regions; however, anti-PbMdj1 did not affect fungal growth in the concentrations tested in vitro, possibly due to the poor access of the antibodies to their target in growing cells. Labeled mitochondria stood preferentially close to the plasma membrane, and gold particles were detected in the thin space between them, toward the cell surface. We show that Mdj1 and the mitochondrial proteinase Lon homologues are heat shock proteins in P. brasiliensis and that their gene organizations are conserved among thermodimorphic fungi and Aspergillus, where the genes are adjacent and have a common 5′ region. This is the first time a DnaJ member has been observed on the cell surface, where its function is speculative.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wanzhen Su ◽  
Jialin Liu ◽  
Peng Bai ◽  
Baocang Ma ◽  
Wei Liu

Abstract Background Since animals frequently encounter a variety of harmful fungi in nature, their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted the significant involvement of indigenous microbial communities in human health. However, the daunting diversity of mammalian microbiota and host genetic complexity are major obstacles to our understanding of these intricate links between microbiota components, host immune genotype, and disease phenotype. In this study, we sought to develop a bacterium-fungus-Drosophila model to systematically evaluate the anti-fungal effects of commensal bacteria. Results We isolated the pathogenic fungal strain, Diaporthe FY, which was detrimental to the survival and development of Drosophila upon infection. Using Drosophila as a model system, Drosophila-associated Lactobacillus plantarum functioned as a probiotic, and protected the flies from mortality induced by Diaporthe FY. Our results show that L. plantarum hindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, consequently mitigating the toxicity of Diaporthe FY to the hosts. Additionally, the presence of L. plantarum overrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions Diaporthe FY was identified as a potential Drosophila pathogen. Commensal L. plantarum mitigated the susceptibility of Drosophila to pathogenic fungi, providing insight into the natural interplay between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis.


mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Kylie J. Boyce ◽  
David P. De Souza ◽  
Saravanan Dayalan ◽  
Shivani Pasricha ◽  
Dedreia Tull ◽  
...  

ABSTRACTFungi are adept at occupying specific environmental niches and often exploit numerous secondary metabolites generated by the cytochrome P450 (CYP) monoxygenases. This report describes the characterization of a yeast-specific CYP encoded bysimA("survivalinmacrophages"). Deletion ofsimAdoes not affect yeast growth at 37°Cin vitrobut is essential for yeast cell production during macrophage infection. The ΔsimAstrain exhibits reduced conidial germination and intracellular growth of yeast in macrophages, suggesting that the enzymatic product of SimA is required for normal fungal growthin vivo. Intracellular ΔsimAyeast cells exhibit cell wall defects, and metabolomic and chemical sensitivity data suggest that SimA may promote chitin synthesis or depositionin vitro.In vivo, ΔsimAyeast cells subsequently lyse and are degraded, suggesting that SimA may increase resistance to and/or suppress host cell biocidal effectors. The results suggest thatsimAsynthesizes a secondary metabolite that allowsT. marneffeito occupy the specific intracellular environmental niche within the macrophage.IMPORTANCEThis study in a dimorphic fungal pathogen uncovered a role for a yeast-specific cytochrome P450 (CYP)-encoding gene in the ability ofT. marneffeito grow as yeast cells within the host macrophages. This report will inspire further research into the role of CYPs and secondary metabolite synthesis during fungal pathogenic growth.


2019 ◽  
Author(s):  
Wanzhen Su ◽  
Jialin Liu ◽  
Peng Bai ◽  
Baocang Ma ◽  
Wei Liu

Abstract Background Since animals frequently encounter a variety of harmful fungi in nature, their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted the significant involvement of indigenous microbial communities in human health. However, the daunting diversity of mammalian microbiota and host genetic complexity are major obstacles to our understanding of these intricate links between microbiota components, host immune genotype, and disease phenotype. In this study, we sought to develop a bacterium-fungus-Drosophilamodel to systematically evaluate the anti-fungal effects of commensal bacteria. Results We isolated the pathogenic fungal strain, Diaporthe FY, which was detrimental to the survival and development of Drosophilaupon infection. Using Drosophilaas a model system, Drosophila-associatedLactobacillus plantarumfunctioned as a probiotic, and protected the flies from mortality induced by Diaporthe FY. Our results show that L. plantarumhindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, consequently mitigating the toxicity of Diaporthe FY to the hosts. Additionally, the presence of L. plantarumoverrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions Diaporthe FY was identified as a potential Drosophila pathogen. Commensal L. plantarummitigated the susceptibility of Drosophilato pathogenic fungi, providing insight into the natural interplay between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis. Keywords L. plantarum, fungal infection, Drosophila, antagonist, oviposition.


2019 ◽  
Author(s):  
Wanzhen Su ◽  
Jialin Liu ◽  
Peng Bai ◽  
Baocang Ma ◽  
Wei Liu

Abstract Background Since animals frequently encounter a variety of harmful fungi in nature, their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted the significant involvement of indigenous microbial communities in human health. However, the daunting diversity of mammalian microbiota and host genetic complexity are major obstacles to our understanding of these intricate links between microbiota components, host immune genotype, and disease phenotype. In this study, we sought to develop a bacterium-fungus-Drosophilamodel to systematically evaluate the anti-fungal effects of commensal bacteria. Results We isolated the pathogenic fungal strain, Diaporthe FY, which was detrimental to the survival and development of Drosophilaupon infection. Using Drosophilaas a model system, Drosophila-associatedLactobacillus plantarumfunctioned as a probiotic, and protected the flies from mortality induced by Diaporthe FY. Our results show that L. plantarumhindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, consequently mitigating the toxicity of Diaporthe FY to the hosts. Additionally, the presence of L. plantarumoverrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions Diaporthe FY was identified as a potential Drosophila pathogen. Commensal L. plantarummitigated the susceptibility of Drosophilato pathogenic fungi, providing insight into the natural interplay between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis. Keywords L. plantarum, fungal infection, Drosophila, antagonist, oviposition.


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