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Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion.
Laure Nicolas Annick Ries; Patricia Alves de Castro; Lilian Pereira Silva; Clara Valero; Thaila Fernanda dos Reis; Raquel Saborano; Iola F. Duarte; Gabriela Felix Persinoti; Jacob L. Steenwyk; Antonis Rokas; Fausto Almeida; Jonas Henrique Costa; Taicia Fill; Sarah Sze Wah Wong; Vishukumar Aimanianda; Fernando José Santos Rodrigues; Relber A. Gonçales; Cláudio Duarte-Oliveira; Agostinho Carvalho; Gustavo H. Goldman. Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity. mBio 2021, e0168221 .
AMA StyleLaure Nicolas Annick Ries, Patricia Alves de Castro, Lilian Pereira Silva, Clara Valero, Thaila Fernanda dos Reis, Raquel Saborano, Iola F. Duarte, Gabriela Felix Persinoti, Jacob L. Steenwyk, Antonis Rokas, Fausto Almeida, Jonas Henrique Costa, Taicia Fill, Sarah Sze Wah Wong, Vishukumar Aimanianda, Fernando José Santos Rodrigues, Relber A. Gonçales, Cláudio Duarte-Oliveira, Agostinho Carvalho, Gustavo H. Goldman. Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity. mBio. 2021; ():e0168221.
Chicago/Turabian StyleLaure Nicolas Annick Ries; Patricia Alves de Castro; Lilian Pereira Silva; Clara Valero; Thaila Fernanda dos Reis; Raquel Saborano; Iola F. Duarte; Gabriela Felix Persinoti; Jacob L. Steenwyk; Antonis Rokas; Fausto Almeida; Jonas Henrique Costa; Taicia Fill; Sarah Sze Wah Wong; Vishukumar Aimanianda; Fernando José Santos Rodrigues; Relber A. Gonçales; Cláudio Duarte-Oliveira; Agostinho Carvalho; Gustavo H. Goldman. 2021. "Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity." mBio , no. : e0168221.
Aspergillus fumigatus is the main causative agent of invasive pulmonary aspergillosis (IPA), a severe disease that affects immunosuppressed patients worldwide. The fungistatic drug caspofungin is the second line therapy against IPA but has increasingly been used against clinical strains that are resistant to azoles, the first line antifungal therapy. In high concentrations, caspofungin induces a tolerance phenotype with partial reestablishment of fungal growth called caspofungin paradoxical effect (CPE), resulting from a change in the composition of the cell wall. An increasing number of studies has shown that different isolates of A. fumigatus exhibit phenotypic heterogeneity, including heterogeneity in their CPE response. To gain insights into the underlying molecular mechanisms of CPE response heterogeneity, we analyzed the transcriptomes of two A. fumigatus reference strains, Af293 and CEA17, exposed to low and high caspofungin concentrations. We found that there is a core transcriptional response that involves genes related to cell wall remodeling processes, mitochondrial function, transmembrane transport, and amino acid and ergosterol metabolism, and a variable response related to secondary metabolite (SM) biosynthesis and iron homeostasis. Specifically, we show here that the overexpression of a SM pathway that works as an iron chelator extinguishes the CPE in both backgrounds, whereas iron depletion is detrimental for the CPE in Af293 but not in CEA17. We next investigated the function of the transcription factor CrzA, whose deletion was previously shown to result in heterogeneity in the CPE response of the Af293 and CEA17 strains. We found that CrzA constitutively binds to and modulates the expression of several genes related to processes involved in caspofungin tolerance, and that crzA deletion differentially impacts the SM production and growth of Af293 and CEA17. As opposed to the ΔcrzA CEA17 mutant, the ΔcrzA Af293 mutant fails to activate cell wall remodeling genes upon caspofungin exposure, which most likely severely affects its macrostructure and extinguishes its CPE. This work describes how heterogeneity in the response to an antifungal agent between A. fumigatus strains stems from heterogeneity in the function of a transcription factor and its downstream target genes.
Ana Cristina Colabardini; Fang Wang; Zhiqiang Dong; Lakhansing Pardeshi; Marina Campos Rocha; Jonas Henrique Costa; Thaila Fernanda dos Reis; Alec Brown; Qais Z. Jaber; Micha Fridman; Taicia Fill; Antonis Rokas; Iran Malavazi; Koon Ho Wong; Gustavo Henrique Goldman. Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin. 2021, 1 .
AMA StyleAna Cristina Colabardini, Fang Wang, Zhiqiang Dong, Lakhansing Pardeshi, Marina Campos Rocha, Jonas Henrique Costa, Thaila Fernanda dos Reis, Alec Brown, Qais Z. Jaber, Micha Fridman, Taicia Fill, Antonis Rokas, Iran Malavazi, Koon Ho Wong, Gustavo Henrique Goldman. Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin. . 2021; ():1.
Chicago/Turabian StyleAna Cristina Colabardini; Fang Wang; Zhiqiang Dong; Lakhansing Pardeshi; Marina Campos Rocha; Jonas Henrique Costa; Thaila Fernanda dos Reis; Alec Brown; Qais Z. Jaber; Micha Fridman; Taicia Fill; Antonis Rokas; Iran Malavazi; Koon Ho Wong; Gustavo Henrique Goldman. 2021. "Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin." , no. : 1.
Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolised via different pathways in A. fumigatus and that acetate utilisation is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilisation is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, to anti-fungal drugs and to human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilisation in A. fumigatus and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of anti-fungal strategies.
Laure Nicolas Annick Ries; Patricia Alves de Castro; Lilian Pereira Silva; Clara Valero; Thaila Fernanda dos Reis; Raquel Saborano; Iola F. Duarte; Gabriela Felix Persinoti; Jacob L. Steenwyk; Antonis Rokas; Fausto Almeida; Jonas Henrique Costa; Taicia Pacheco Fill; Sarah Sze Wah Wong; Vishukumar Aimanianda; Fernando José Santos Rodrigues; Relber Aguiar Gonçales; Claudio Duarte-Oliveira; Agostinho Carvalho; Gustavo H. Goldman. Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity. 2021, 1 .
AMA StyleLaure Nicolas Annick Ries, Patricia Alves de Castro, Lilian Pereira Silva, Clara Valero, Thaila Fernanda dos Reis, Raquel Saborano, Iola F. Duarte, Gabriela Felix Persinoti, Jacob L. Steenwyk, Antonis Rokas, Fausto Almeida, Jonas Henrique Costa, Taicia Pacheco Fill, Sarah Sze Wah Wong, Vishukumar Aimanianda, Fernando José Santos Rodrigues, Relber Aguiar Gonçales, Claudio Duarte-Oliveira, Agostinho Carvalho, Gustavo H. Goldman. Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity. . 2021; ():1.
Chicago/Turabian StyleLaure Nicolas Annick Ries; Patricia Alves de Castro; Lilian Pereira Silva; Clara Valero; Thaila Fernanda dos Reis; Raquel Saborano; Iola F. Duarte; Gabriela Felix Persinoti; Jacob L. Steenwyk; Antonis Rokas; Fausto Almeida; Jonas Henrique Costa; Taicia Pacheco Fill; Sarah Sze Wah Wong; Vishukumar Aimanianda; Fernando José Santos Rodrigues; Relber Aguiar Gonçales; Claudio Duarte-Oliveira; Agostinho Carvalho; Gustavo H. Goldman. 2021. "Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity." , no. : 1.
Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.
Marcos Silva; Jonas Costa; Taícia Pacheco-Fill; Ana Ruiz; Flávia Vidal; Kátia Borges; Sulayne Guimarães; Ana Azevedo-Santos; Kaio Buglio; Mary Foglio; Maria Barbosa; Maria Nascimento; João de Carvalho. Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line. Molecules 2021, 26, 3546 .
AMA StyleMarcos Silva, Jonas Costa, Taícia Pacheco-Fill, Ana Ruiz, Flávia Vidal, Kátia Borges, Sulayne Guimarães, Ana Azevedo-Santos, Kaio Buglio, Mary Foglio, Maria Barbosa, Maria Nascimento, João de Carvalho. Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line. Molecules. 2021; 26 (12):3546.
Chicago/Turabian StyleMarcos Silva; Jonas Costa; Taícia Pacheco-Fill; Ana Ruiz; Flávia Vidal; Kátia Borges; Sulayne Guimarães; Ana Azevedo-Santos; Kaio Buglio; Mary Foglio; Maria Barbosa; Maria Nascimento; João de Carvalho. 2021. "Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line." Molecules 26, no. 12: 3546.
Penicillium digitatum is the most aggressive pathogen of citrus fruits. Tryptoquialanines are major indole alkaloids produced by P. digitatum. It is unknown if tryptoquialanines are involved in the damage of citrus fruits caused by P. digitatum. To investigate the pathogenic roles of tryptoquialanines, we initially asked if tryptoquialanines could affect the germination of Citrus sinensis seeds. Exposure of the citrus seeds to tryptoquialanine A resulted in a complete inhibition of germination and an altered metabolic response. Since this phytotoxic effect requires the extracellular export of tryptoquialanine A, we investigated the mechanisms of extracellular delivery of this alkaloid in P. digitatum. We detected extracellular vesicles (EVs) released by P. digitatum both in culture and during infection of citrus fruits. Compositional analysis of EVs produced during infection revealed the presence of a complex cargo, which included tryptoquialanines and the mycotoxin fungisporin. The EVs also presented phytotoxicity activity in vitro and caused damage to the tissues of citrus seeds. Through molecular networking, it was observed that the metabolites present in the P. digitatum EVs are produced in all of its possible hosts. Our results reveal a novel phytopathogenic role of P. digitatum EVs and tryptoquialanine A, implying that this alkaloid is exported in EVs during plant infection. IMPORTANCE During the postharvest period, citrus fruits can be affected by phytopathogens such as Penicillium digitatum, which causes green mold disease and is responsible for up to 90% of total citrus losses. Chemical fungicides are widely used to prevent green mold disease, leading to concerns about environmental and health risks. To develop safer alternatives to control phytopathogens, it is necessary to understand the molecular basis of infection during the host-pathogen interaction. In the P. digitatum model, the virulence strategies are poorly known. Here, we describe the production of phytotoxic extracellular vesicles (EVs) by P. digitatum during the infection of citrus fruits. We also characterized the secondary metabolites in the cargo of EVs and found in this set of molecules an inhibitor of seed germination. Since EVs and secondary metabolites have been related to virulence mechanisms in other host-pathogen interactions, our data are important for the comprehension of how P. digitatum causes damage to its primary hosts.
Jonas Henrique Costa; Jaqueline Moraes Bazioli; Luidy Darllan Barbosa; Pedro Luis Theodoro Dos Santos Júnior; Flavia C. G. Reis; Tabata Klimeck; Camila Manoel Crnkovic; Roberto G. S. Berlinck; Alessandra Sussulini; Marcio L. Rodrigues; Taícia Pacheco Fill. Phytotoxic Tryptoquialanines Produced In Vivo by Penicillium digitatum Are Exported in Extracellular Vesicles. mBio 2021, 12, 1 .
AMA StyleJonas Henrique Costa, Jaqueline Moraes Bazioli, Luidy Darllan Barbosa, Pedro Luis Theodoro Dos Santos Júnior, Flavia C. G. Reis, Tabata Klimeck, Camila Manoel Crnkovic, Roberto G. S. Berlinck, Alessandra Sussulini, Marcio L. Rodrigues, Taícia Pacheco Fill. Phytotoxic Tryptoquialanines Produced In Vivo by Penicillium digitatum Are Exported in Extracellular Vesicles. mBio. 2021; 12 (1):1.
Chicago/Turabian StyleJonas Henrique Costa; Jaqueline Moraes Bazioli; Luidy Darllan Barbosa; Pedro Luis Theodoro Dos Santos Júnior; Flavia C. G. Reis; Tabata Klimeck; Camila Manoel Crnkovic; Roberto G. S. Berlinck; Alessandra Sussulini; Marcio L. Rodrigues; Taícia Pacheco Fill. 2021. "Phytotoxic Tryptoquialanines Produced In Vivo by Penicillium digitatum Are Exported in Extracellular Vesicles." mBio 12, no. 1: 1.
Penicillium digitatum is the most aggressive pathogen of citrus fruits. Tryptoquialanines are major indole alkaloids produced by P. digitatum. It is unknown if tryptoquialanines are involved in the damage of citrus fruits caused by P. digitatum. To investigate the pathogenic roles of tryptoquialanines, we initially asked if tryptoquialanines could affect the germination of Citrus sinensis seeds. Exposure of the citrus seeds to tryptoquialanine A resulted in a complete inhibition of germination and an altered metabolic response. Since this phytotoxic effect requires the extracellular export of tryptoquialanine A, we investigated the mechanisms of extracellular delivery of this alkaloid in P. digitatum. We detected extracellular vesicles (EVs) released by P. digitatum both in culture and during infection of citrus fruits. Compositional analysis of EVs produced during infection revealed the presence of a complex cargo, which included tryptoquialanines and the mycotoxin fungisporin. The EVs also presented phytotoxicity activity in vitro, and caused damage to the tissues of citrus seeds. Through molecular networking, it was observed that the metabolites present in the P. digitatum EVs are produced in all of its possible hosts. Our results reveal a novel phytopathogenic role of P. digitatum EVs and tryptoquialanine A, implying that this alkaloid is exported in EVs during plant infection. IMPORTANCE During the post-harvest period, citrus fruits can be affected by phytopathogens such as Penicillium digitatum, which causes the green mold disease and is responsible for up to 90 % of the total citrus losses. Chemical fungicides are widely used to prevent the green mold disease, leading to concerns about environmental and health risks. To develop safer alternatives to control phytopathogens, it is necessary to understand the molecular basis of infection during the host-pathogen interaction. In the P. digitatum model, the virulence strategies are poorly known. Here, we describe the production of phytotoxic extracellular vesicles (EVs) by P. digitatum during the infection of citrus fruits. We also characterized the secondary metabolites in the cargo of EVs and found in this set of molecules an inhibitor of seed germination. Since EVs and secondary metabolites have been related to virulence mechanisms in other host-pathogen interactions, our data are important for the comprehension of how P. digitatum causes damage to its primary hosts.
Jonas Henrique Costa; Jaqueline Moraes Bazioli; Luidy Darllan Barbosa; Pedro Luis Theodoro Dos Santos Júnior; Flavia C. G. Reis; Tabata Klimeck; Camila Manoel Crnkovic; Roberto G. S. Berlinck; Alessandra Sussulini; Marcio L. Rodrigues; Taícia Pacheco Fill. Phytotoxic tryptoquialanines produced in vivo by Penicillium digitatum are exported in extracellular vesicles. 2020, 1 .
AMA StyleJonas Henrique Costa, Jaqueline Moraes Bazioli, Luidy Darllan Barbosa, Pedro Luis Theodoro Dos Santos Júnior, Flavia C. G. Reis, Tabata Klimeck, Camila Manoel Crnkovic, Roberto G. S. Berlinck, Alessandra Sussulini, Marcio L. Rodrigues, Taícia Pacheco Fill. Phytotoxic tryptoquialanines produced in vivo by Penicillium digitatum are exported in extracellular vesicles. . 2020; ():1.
Chicago/Turabian StyleJonas Henrique Costa; Jaqueline Moraes Bazioli; Luidy Darllan Barbosa; Pedro Luis Theodoro Dos Santos Júnior; Flavia C. G. Reis; Tabata Klimeck; Camila Manoel Crnkovic; Roberto G. S. Berlinck; Alessandra Sussulini; Marcio L. Rodrigues; Taícia Pacheco Fill. 2020. "Phytotoxic tryptoquialanines produced in vivo by Penicillium digitatum are exported in extracellular vesicles." , no. : 1.
Flavonoids are involved in citrus defense against phytopathogens. In this study, we applied in vitro biocatalysis assays using the flavanones glycosides hesperidin and naringin to explore the enzymatic activities involved in such interaction. The main enzymatic activity observed was the hydrolysis catalyzed by fungi naringinases and hesperidinases. Withing 7 days, the two citrus phytopathogenic fungi, Penicillium digitatum and Penicillium italicum, exhibited the highest hydrolyzing rate on the flavanones, reaching conversion values higher than 90%. In addition, Geothrichum citri-aurantii exhibited no enzymatic activity and Penicillium expansum only hydrolyzed hesperidin. In order to evaluate flavonoid biotransformation by the fungi in vivo, citrus fruits infected with P. digitatum were analyzed through molecular networking and Imaging Mass Spectrometry (IMS). In vivo assays revealed that citrus fruit in response to the infection is able to hydroxylate flavonoids, and novel flavonoid structures were associated to the citrus’ defense. The data reported here present a new point of view in the relation between citrus flavonoids and phytopathogenic fungi and can be useful to understand the infection processes and host-pathogen interaction.
Jonas Henrique Costa; Laura Soler Fernandes; Daniel Yuri Akiyama; Taícia Pacheco Fill. Exploring the interaction between citrus flavonoids and phytopathogenic fungi through enzymatic activities. Bioorganic Chemistry 2020, 102, 104126 .
AMA StyleJonas Henrique Costa, Laura Soler Fernandes, Daniel Yuri Akiyama, Taícia Pacheco Fill. Exploring the interaction between citrus flavonoids and phytopathogenic fungi through enzymatic activities. Bioorganic Chemistry. 2020; 102 ():104126.
Chicago/Turabian StyleJonas Henrique Costa; Laura Soler Fernandes; Daniel Yuri Akiyama; Taícia Pacheco Fill. 2020. "Exploring the interaction between citrus flavonoids and phytopathogenic fungi through enzymatic activities." Bioorganic Chemistry 102, no. : 104126.
Aspergillus fumigatus , one of the most important human-pathogenic fungal species, is able to cause aspergillosis, a heterogeneous group of diseases that presents a wide range of clinical manifestations. Invasive pulmonary aspergillosis is the most serious pathology in terms of patient outcome and treatment, with a high mortality rate ranging from 50% to 95% primarily affecting immunocompromised patients. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, there were several reports of evolution of clinical azole resistance in the last decade. Caspofungin, a noncompetitive β-1,3-glucan synthase inhibitor, has been used against A. fumigatus , but it is fungistatic and is recommended as second-line therapy for invasive aspergillosis. More information about caspofungin tolerance and resistance is necessary in order to refine antifungal strategies that target the fungal cell wall. Here, we screened a transcription factor (TF) deletion library for TFs that can mediate caspofungin tolerance and resistance. We have identified 11 TFs that are important for caspofungin sensitivity and/or for the c aspofungin p aradoxical e ffect (CPE). These TFs encode proteins involved in the basal modulation of the RNA polymerase II initiation sites, calcium metabolism or cell wall remodeling, and mitochondrial respiratory function. The study of those genes regulated by TFs identified in this work will provide a better understanding of the signaling pathways that are important for caspofungin tolerance and resistance.
Clara Valero; Ana Cristina Colabardini; Jéssica Chiaratto; Lakhansing Pardeshi; Patrícia Alves de Castro; Jaire Alves Ferreira Filho; Lilian Pereira Silva; Marina Campos Rocha; Iran Malavazi; Jonas Henrique Costa; Taícia Fill; Mário Henrique Barros; Sarah Sze Wah Wong; Vishukumar Aimanianda; Koon Ho Wong; Gustavo H. Goldman. Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect. mBio 2020, 11, 1 .
AMA StyleClara Valero, Ana Cristina Colabardini, Jéssica Chiaratto, Lakhansing Pardeshi, Patrícia Alves de Castro, Jaire Alves Ferreira Filho, Lilian Pereira Silva, Marina Campos Rocha, Iran Malavazi, Jonas Henrique Costa, Taícia Fill, Mário Henrique Barros, Sarah Sze Wah Wong, Vishukumar Aimanianda, Koon Ho Wong, Gustavo H. Goldman. Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect. mBio. 2020; 11 (3):1.
Chicago/Turabian StyleClara Valero; Ana Cristina Colabardini; Jéssica Chiaratto; Lakhansing Pardeshi; Patrícia Alves de Castro; Jaire Alves Ferreira Filho; Lilian Pereira Silva; Marina Campos Rocha; Iran Malavazi; Jonas Henrique Costa; Taícia Fill; Mário Henrique Barros; Sarah Sze Wah Wong; Vishukumar Aimanianda; Koon Ho Wong; Gustavo H. Goldman. 2020. "Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect." mBio 11, no. 3: 1.
Most of the biosynthetic gene clusters (BGCs) found in filamentous fungi are silent under standard laboratory cultivation conditions due to the lack of expression triggering stimuli, representing a considerable drawback in drug discovery. To access the full biosynthetic potential of these microbes, studies towards the activation of cryptic BGCs are essential. Histone acetylation status is an important regulator of chromatin structure which impacts in cell physiology and, therefore, expression of biosynthetic gene clusters in filamentous fungi. Histone deacetylases (HDACs) and histone acetyl-transferases (HATs) are responsible for maintaining and controlling this process under different cell conditions. In this study, clr3, a gene encoding a histone deacetylase in Penicillium brasilianum was deleted and associated phenotypic and metabolic changes evaluated. Results indicate reduced growth under oxidative stress conditions in the Δclr3 knockout strain. Also, the production of several secondary metabolites including austin-related meroterpenoids, brasiliamides, mycotoxins such as verruculogen and penicillic acid, as well as cyclodepsipeptides was reduced in the Δclr3 strain when compared to wild-type strain. Accordingly, addition of epigenetic modulators responsible for HDAC inhibition such as suberoylanilide hydroxamic acid (SAHA) and nicotinamide (NAA) to P. brasilianum growth media also culminated in reduction of secondary metabolite production. Mass Spectrometry Imaging (MSI) was applied to compare metabolite production and spatial distribution on the colony. Results suggest that Clr3 plays an important role in secondary metabolite biosynthesis in P. brasilianum, thus offering new strategies for regulation of natural product synthesis by assessing chromatin modification in P. brasilianum.
Daniel Yuri Akiyama; Marina Campos Rocha; Jonas Henrique Costa; Iran Malavazi; Taicia Pacheco Fill. The histone deacetylase clr3 regulates secondary metabolite production and growth under oxidative stress conditions in Penicillium brasilianum. 2020, 1 .
AMA StyleDaniel Yuri Akiyama, Marina Campos Rocha, Jonas Henrique Costa, Iran Malavazi, Taicia Pacheco Fill. The histone deacetylase clr3 regulates secondary metabolite production and growth under oxidative stress conditions in Penicillium brasilianum. . 2020; ():1.
Chicago/Turabian StyleDaniel Yuri Akiyama; Marina Campos Rocha; Jonas Henrique Costa; Iran Malavazi; Taicia Pacheco Fill. 2020. "The histone deacetylase clr3 regulates secondary metabolite production and growth under oxidative stress conditions in Penicillium brasilianum." , no. : 1.
The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL−1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.
Jaqueline Moraes Bazioli; Jonas Henrique Costa; Larissa Shiozawa; Ana Lúcia Tasca Gois Ruiz; Mary Ann Foglio; João Ernesto De Carvalho. Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.). Molecules 2020, 25, 1525 .
AMA StyleJaqueline Moraes Bazioli, Jonas Henrique Costa, Larissa Shiozawa, Ana Lúcia Tasca Gois Ruiz, Mary Ann Foglio, João Ernesto De Carvalho. Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.). Molecules. 2020; 25 (7):1525.
Chicago/Turabian StyleJaqueline Moraes Bazioli; Jonas Henrique Costa; Larissa Shiozawa; Ana Lúcia Tasca Gois Ruiz; Mary Ann Foglio; João Ernesto De Carvalho. 2020. "Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.)." Molecules 25, no. 7: 1525.
Numerous postharvest diseases have been reported that cause substantial losses of citrus fruits worldwide. Penicillium digitatum is responsible for up to 90% of production losses, and represent a problem for worldwide economy. In order to control phytopathogens, chemical fungicides have been extensively used. Yet, the use of some artificial fungicides cause concerns about environmental risks and fungal resistance. Therefore, studies focusing on new approaches, such as the use of natural products, are getting attention. Co-culture strategy can be applied to discover new bioactive compounds and to understand microbial ecology. Mass Spectrometry Imaging (MSI) was used to screen for potential antifungal metabolites involved in the interaction between Penicillium digitatum and Penicillium citrinum. MSI revealed a chemical warfare between the fungi: two tetrapeptides, deoxycitrinadin A, citrinadin A, chrysogenamide A and tryptoquialanines are produced in the fungi confrontation zone. Antimicrobial assays confirmed the antifungal activity of the investigated metabolites. Also, tryptoquialanines inhibited sporulation of P. citrinum. The fungal metabolites reported here were never described as antimicrobials until this date, demonstrating that co-cultures involving phytopathogens that compete for the same host is a positive strategy to discover new antifungal agents. However, the use of these natural products on the environment, as a safer strategy, needs further investigation. This paper aimed to contribute to the protection of agriculture, considering health and ecological risks.
Jonas Henrique Costa; Cristiane Izumi Wassano; Célio Fernando Figueiredo Angolini; Kirstin Scherlach; Christian Hertweck; Taícia Pacheco Fill. Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens. Scientific Reports 2019, 9, 1 -11.
AMA StyleJonas Henrique Costa, Cristiane Izumi Wassano, Célio Fernando Figueiredo Angolini, Kirstin Scherlach, Christian Hertweck, Taícia Pacheco Fill. Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens. Scientific Reports. 2019; 9 (1):1-11.
Chicago/Turabian StyleJonas Henrique Costa; Cristiane Izumi Wassano; Célio Fernando Figueiredo Angolini; Kirstin Scherlach; Christian Hertweck; Taícia Pacheco Fill. 2019. "Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens." Scientific Reports 9, no. 1: 1-11.
Citrus are vulnerable to the postharvest decay caused by Penicillium digitatum, Penicillium italicum, and Geotrichum citri-aurantii, which are responsible for the green mold, blue mold, and sour rot post-harvest disease, respectively. The widespread economic losses in citriculture caused by these phytopathogens are minimized with the use of synthetic fungicides such as imazalil, thiabendazole, pyrimethanil, and fludioxonil, which are mainly employed as control agents and may have harmful effects on human health and environment. To date, numerous non-chemical postharvest treatments have been investigated for the control of these pathogens. Several studies demonstrated that biological control using microbial antagonists and natural products can be effective in controlling postharvest diseases in citrus, as well as the most used commercial fungicides. Therefore, microbial agents represent a considerably safer and low toxicity alternative to synthetic fungicides. In the present review, these biological control strategies as alternative to the chemical fungicides are summarized here and new challenges regarding the development of shelf-stable formulated biocontrol products are also discussed.
Jaqueline Moraes Bazioli; João Raul Belinato; Jonas Henrique Costa; Daniel Yuri Akiyama; João Guilherme De Moraes Pontes; Katia Cristina Kupper; Fabio Augusto; João Ernesto De Carvalho; Taícia Pacheco Fill. Biological Control of Citrus Postharvest Phytopathogens. Toxins 2019, 11, 460 .
AMA StyleJaqueline Moraes Bazioli, João Raul Belinato, Jonas Henrique Costa, Daniel Yuri Akiyama, João Guilherme De Moraes Pontes, Katia Cristina Kupper, Fabio Augusto, João Ernesto De Carvalho, Taícia Pacheco Fill. Biological Control of Citrus Postharvest Phytopathogens. Toxins. 2019; 11 (8):460.
Chicago/Turabian StyleJaqueline Moraes Bazioli; João Raul Belinato; Jonas Henrique Costa; Daniel Yuri Akiyama; João Guilherme De Moraes Pontes; Katia Cristina Kupper; Fabio Augusto; João Ernesto De Carvalho; Taícia Pacheco Fill. 2019. "Biological Control of Citrus Postharvest Phytopathogens." Toxins 11, no. 8: 460.
A method was developed and validated for determination of tryptoquialanines A and C in orange samples on epicarp (exterior peel), mesocarp (white peel), and endocarp (fruit juice) based on QuEChERS extraction and LC-MS/MS analysis. The method showed an excellent linearity over a range of 5–400 μg kg−1, with r2 ≥ 0.998. The limits of detection (LOD) and quantification (LOQ) were 5 and 10 µg kg−1, respectively. Recoveries showed values between 57 and 101%, with RSD ≤ 12%. Analysis of infected oranges showed diffusion of the alkaloids between the orange layers after 4 days post infection in concentrations > LOQ. Mycotoxin diffusion to healthy oranges after direct contact with infected oranges for 48 h, showed alkaloid concentrations ≥10 µg kg−1 on epicarp layer. The developed method can be easily applied for quality control in routine analysis of orange fruit due to the high risk that these tremorgenic alkaloids represent to human health.
Éder De Vilhena Araújo; Pedro Henrique Vendramini; Jonas Henrique Costa; Marcos Nogueira Eberlin; Cassiana Carolina Montagner; Taicia Pacheco Fill. Determination of tryptoquialanines A and C produced by Penicillium digitatum in oranges: Are we safe? Food Chemistry 2019, 301, 125285 .
AMA StyleÉder De Vilhena Araújo, Pedro Henrique Vendramini, Jonas Henrique Costa, Marcos Nogueira Eberlin, Cassiana Carolina Montagner, Taicia Pacheco Fill. Determination of tryptoquialanines A and C produced by Penicillium digitatum in oranges: Are we safe? Food Chemistry. 2019; 301 ():125285.
Chicago/Turabian StyleÉder De Vilhena Araújo; Pedro Henrique Vendramini; Jonas Henrique Costa; Marcos Nogueira Eberlin; Cassiana Carolina Montagner; Taicia Pacheco Fill. 2019. "Determination of tryptoquialanines A and C produced by Penicillium digitatum in oranges: Are we safe?" Food Chemistry 301, no. : 125285.
Penicillium digitatum is the major source of postharvest decay in citrus fruits worldwide. This fungus shows a notably limited host range, being able to infect mainly mature fruit belonging to the Rutaceae family. This highly specific host interaction has attracted the interest of the scientific community. Researchers have investigated the chemical interactions and specialized virulence strategies that facilitate this fungus’s fruit colonization, thereby leading to a successful citrus infection. There are several factors that mediate and affect the interaction between Penicillium digitatum and its host citrus, including hydrogen peroxide modulation by the phytopathogen, secretion of organic acids and consequently pH control, and other strategies described in this review. The recently achieved sequencing of the complete Penicillium digitatum genome opened up new possibilities for exploration of the virulence factors related to the host-pathogen interaction. Through such techniques as RNAseq, RT-PCR and targeted gene knockout mediated by Agrobacterium tumefaciens, important genes involved in the fungal infection process in citrus have been reported, helping to elucidate the molecular mechanisms, metabolites and genetic components that are involved in the pathogenicity of P. digitatum. Understanding the infection process and fungal strategies represents an important step in developing ways to protect citrus from Penicillium digitatum infection, possibly leading to more productive citriculture worldwide.
Jonas Henrique Costa; Jaqueline Moraes Bazioli; João Guilherme De Moraes Pontes; Taícia Pacheco Fill. Penicillium digitatum infection mechanisms in citrus: What do we know so far? Fungal Biology 2019, 123, 584 -593.
AMA StyleJonas Henrique Costa, Jaqueline Moraes Bazioli, João Guilherme De Moraes Pontes, Taícia Pacheco Fill. Penicillium digitatum infection mechanisms in citrus: What do we know so far? Fungal Biology. 2019; 123 (8):584-593.
Chicago/Turabian StyleJonas Henrique Costa; Jaqueline Moraes Bazioli; João Guilherme De Moraes Pontes; Taícia Pacheco Fill. 2019. "Penicillium digitatum infection mechanisms in citrus: What do we know so far?" Fungal Biology 123, no. 8: 584-593.
Green mold, caused by Penicillium digitatum, is the most destructive post-harvest disease in citrus. Secondary metabolites produced by fungal phytopathogens have been associated with toxicity to their respective host through the interaction with a wide range of cell targets. Natural products have also been described as important molecules for biocontrol and competion in their respective environment. For P. digitatum, the production of indole alkaloids, tryptoquialanines A and B, have been reported. However, their biological role remains unknown. Mass Spectrometry Imaging (MSI) technique was applied here for the first time to monitor the secondary metabolites produced on the orange surface during infection in order to gain insights about the P. digitatum-citrus interaction mechanisms. Through the combination of MSI and molecular networking it was possible to report, for the first time, the production of tryptoquivalines and fumiquinazolines by P. digitatum and also the accumulation of tryptoquialanines on the fruit surface from 4 to 7 days post inoculation. P. digitatum was also evaluated concerning the ability to sinthesize indole alkaloids in vivo in the different citrus hosts. The biological role of tryptoquialanines was investigated and tryptoquialanine A was submitted to insecticidal bioassays that revealed its high toxicity against Aedes Aegypti, suggesting an important insecticidal action during orange decay.
Jonas Henrique Costa; Jaqueline Moraes Bazioli; Eder De Vilhena Araújo; Pedro Henrique Vendramini; Mariana Cristina De Freitas Porto; Marcos Nogueira Eberlin; Jayme A. Souza-Neto; Taícia Pacheco Fill. Monitoring indole alkaloid production by Penicillium digitatum during infection process in citrus by Mass Spectrometry Imaging and molecular networking. Fungal Biology 2019, 123, 594 -600.
AMA StyleJonas Henrique Costa, Jaqueline Moraes Bazioli, Eder De Vilhena Araújo, Pedro Henrique Vendramini, Mariana Cristina De Freitas Porto, Marcos Nogueira Eberlin, Jayme A. Souza-Neto, Taícia Pacheco Fill. Monitoring indole alkaloid production by Penicillium digitatum during infection process in citrus by Mass Spectrometry Imaging and molecular networking. Fungal Biology. 2019; 123 (8):594-600.
Chicago/Turabian StyleJonas Henrique Costa; Jaqueline Moraes Bazioli; Eder De Vilhena Araújo; Pedro Henrique Vendramini; Mariana Cristina De Freitas Porto; Marcos Nogueira Eberlin; Jayme A. Souza-Neto; Taícia Pacheco Fill. 2019. "Monitoring indole alkaloid production by Penicillium digitatum during infection process in citrus by Mass Spectrometry Imaging and molecular networking." Fungal Biology 123, no. 8: 594-600.
High-throughput screening detected transaminases (TAs) and monoamine oxidases (MAOs) in fungi by applying a fluorogenic probe. Strains F026, F037, F041, F053, and F057 showed the highest enzymatic conversions (31, 60, 30, 40, and 32%, respectively) and where evaluated for their ability to transform piperidines. Strain F053 (Neopestalotiopsis sp. CBMAI 2030) revealed unusual enzymatic activity to deracemize 2-methyl-6-alkylpiperidines. Neopestalotiopsis sp. CBMAI 2030 was capable to convert 2-methyl-6-propylpiperidine, 2-methyl-6-butylpiperidine, and 2-methyl-6-pentylpiperidine in piperideine with 11, 14, and 24% conversion, respectively. The activity was enhanced by cultivating the fungus with 2-methyl-6-pentylpiperidine (38% conversion and 73% ee).
Jonas Henrique Costa; Bruna Zucoloto Da Costa; Derlene Attili-Angelis; Anita Jocelyne Marsaioli. Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030. Applied Microbiology and Biotechnology 2017, 101, 6061 -6070.
AMA StyleJonas Henrique Costa, Bruna Zucoloto Da Costa, Derlene Attili-Angelis, Anita Jocelyne Marsaioli. Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030. Applied Microbiology and Biotechnology. 2017; 101 (15):6061-6070.
Chicago/Turabian StyleJonas Henrique Costa; Bruna Zucoloto Da Costa; Derlene Attili-Angelis; Anita Jocelyne Marsaioli. 2017. "Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030." Applied Microbiology and Biotechnology 101, no. 15: 6061-6070.