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Article ; Online: Dectin-2 is critical for phagocyte function and resistance to Paracoccidioides brasiliensis in mice.

Cardoso-Miguel, Mariana de Resende Damas / Bürgel, Pedro Henrique / de Castro, Raffael Júnio Araújo / Marina, Clara Luna / de Oliveira, Stephan Alberto / Albuquerque, Patrícia / Silva-Pereira, Ildinete / Bocca, Anamélia Lorenzetti / Tavares, Aldo Henrique

Medical mycology

2023 Volume 61, Issue 11

Abstract: Germline-encoded pattern recognition receptors, particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs, Dectin-2 (encoded by Clec4n) plays a critical role in the antifungal immune response as ... ...

Abstract	Germline-encoded pattern recognition receptors, particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs, Dectin-2 (encoded by Clec4n) plays a critical role in the antifungal immune response as it recognizes high-mannose polysaccharides on the fungal cell wall, triggering phagocyte functional activities and ultimately determining adaptive responses. Here, we assessed the role of Dectin-2 on the course of primary Paracoccidioides brasiliensis systemic infection in mice with Dectin-2-targeted deletion. Paracoccidioides brasiliensis constitutes the principal etiologic agent of paracoccidioidomycosis, the most prominent invasive mycosis in Latin American countries. The deficiency of Dectin-2 resulted in shortened survival rates, high lung fungal burden, and increased lung pathology in mice infected with P. brasiliensis. Consistently, dendritic cells (DCs) from mice lacking Dectin-2 infected ex vivo with P. brasiliensis showed impaired secretion of several proinflammatory and regulatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10. Additionally, when cocultured with splenic lymphocytes, DCs were less efficient in promoting a type 1 cytokine pattern secretion (i.e., IFN-γ). In macrophages, Dectin-2-mediated signaling was required to ensure phagocytosis and fungicidal activity associated with nitric oxide production. Overall, Dectin-2-mediated signaling is critical to promote host protection against P. brasiliensis infection, and its exploitation might lead to the development of new vaccines and immunotherapeutic approaches.
MeSH term(s)	Mice ; Animals ; Paracoccidioides ; Phagocytes/pathology ; Lectins, C-Type/metabolism ; Macrophages ; Paracoccidioidomycosis/veterinary
Chemical Substances	dectin-2, mouse ; Lectins, C-Type
Language	English
Publishing date	2023-11-14
Publishing country	England
Document type	Journal Article
ZDB-ID	1421796-x
ISSN	1460-2709 ; 1369-3786
ISSN (online)	1460-2709
ISSN	1369-3786
DOI	10.1093/mmy/myad117
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Article: The role of Cryptococcus neoformans histone deacetylase genes in the response to antifungal drugs, epigenetic modulators and to photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion in vitro

Ranjan, Kunal / Brandão, Fabiana / Morais, José Athayde V / Muehlmann, Luís Alexandre / Silva-Pereira, Ildinete / Bocca, Anamélia Lorenzetti / Matos, Larissa Fernandes / Poças-Fonseca, Marcio José

Journal of photochemistry and photobiology. 2021 Mar., v. 216

2021

Abstract: Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of ... ...

Abstract	Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of antifungals allowed the selection of resistant pathogens posing threats to global public health. Histone deacetylase genes are involved in Cryptococcus virulence, and in pathogenicity and resistance to azoles in Candida albicans.Aiming to assess whether histone deacetylase genes are involved in antifungal response and in synergistic drug interactions, we evaluated the activity of amphotericin B, fluconazole, sulfamethoxazole, sodium butyrate or trichostatin A (histone deacetylase inhibitors), and hydralazine or 5- aza-2′-deoxycytidine (DNA methyl-transferase inhibitors) against different Cryptococcus neoformans strains, C. neoformans histone deacetylase null mutants and Cryptococcus gattii NIH198. The drugs were employed alone or in different combinations. Fungal growth after photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion, alone or in combination with the aforementioned drugs, was assessed for the C. neoformans HDAC null mutant strains. Our results showed that fluconazole was synergistic with sodium butyrate or with trichostatin A for the hda1Δ/hos2Δ double mutant strain. Sulfamethoxazole was synergistic with sodium butyrate or with hydralazine also for hda1Δ/hos2Δ. These results clearly indicate a link between HDAC impairment and drug sensitivity. Photodynamic therapy efficacy on controlling the growth of the HDAC mutant strains was increased by amphotericin B, fluconazole, sodium butyrate or hydralazine. This is the first study in Cryptococcus highlighting the combined effects of antifungal drugs, histone deacetylase or DNA methyltransferase inhibitors and photodynamic therapy in vitro.
Keywords	Candida ; Cryptococcus gattii ; Cryptococcus neoformans ; DNA ; DNA methyltransferase ; aluminum ; amphotericin B ; chlorides ; epigenetics ; fluconazole ; fungal growth ; fungi ; histone deacetylase ; mutants ; nanoemulsions ; pathogens ; photobiology ; photochemistry ; photochemotherapy ; public health ; sodium butyrate ; sulfamethoxazole ; virulence
Language	English
Dates of publication	2021-03
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	623022-2
ISSN	1873-2682 ; 1011-1344
ISSN (online)	1873-2682
ISSN	1011-1344
DOI	10.1016/j.jphotobiol.2021.112131
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Simon, Karina Smidt / Coelho, Luísa Coutinho / Veloso, Paulo Henrique de Holanda / Melo-Silva, Cesar Augusto / Morais, José Athayde Vasconcelos / Longo, João Paulo Figueiró / Figueiredo, Florencio / Viana, Leonora / Silva Pereira, Ildinete / Amado, Veronica Moreira / Mortari, Marcia Renata / Bocca, Anamelia Lorenzetti

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.
MeSH term(s)	Mice ; Animals ; Lung/pathology ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/pathology ; Peptides/pharmacology ; Peptides/therapeutic use ; Bleomycin ; Collagen Type I ; Mice, Inbred C57BL
Chemical Substances	Peptides ; Bleomycin (11056-06-7) ; Collagen Type I
Language	English
Publishing date	2023-07-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241311049
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cryptococcus neoformans Database in Synthetic Biology Open Language.

Garcia de Resende, Sophia / Batista, Ana Carolina Campos / Gomide, Mayna da Silveira / Pandolfo, Luis Henrique Scarparo / Ferreira da Silva, Leonardo / Silva-Pereira, Ildinete / Coelho, Cíntia Marques

Microbiology resource announcements

2022 Volume 11, Issue 9, Page(s) e0019822

Abstract: Cryptococcus neoformans is the etiologic agent of cryptococcosis, a lethal worldwide disease. Synthetic biology could contribute to its better understanding through engineering genetic networks. However, its major challenge is the requirement of ... ...

Abstract	Cryptococcus neoformans is the etiologic agent of cryptococcosis, a lethal worldwide disease. Synthetic biology could contribute to its better understanding through engineering genetic networks. However, its major challenge is the requirement of accessible genetic parts. The database presented here provides 23 biological parts for this organism in Synthetic Biology Open Language.
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/mra.00198-22
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Article ; Online: In vitro

Fulgêncio, Débora Luíza Albano / da Costa, Rosiane Andrade / Guilhelmelli, Fernanda / Silva, Calliandra Maria de Souza / Ortega, Daniel Barros / de Araujo, Thiago Fellipe / Silva, Philippe Spezia / Silva-Pereira, Ildinete / Albuquerque, Patrícia / Barreto, Cristine Chaves

AIMS microbiology

2021 Volume 7, Issue 1, Page(s) 28–39

Abstract: Systemic mycoses have become a major cause of morbidity and mortality, particularly among immunocompromised hosts and long-term hospitalized patients. Conventional antifungal agents are limited because of not only their costs and toxicity but also the ... ...

Abstract	Systemic mycoses have become a major cause of morbidity and mortality, particularly among immunocompromised hosts and long-term hospitalized patients. Conventional antifungal agents are limited because of not only their costs and toxicity but also the rise of resistant strains. Lipopeptides from
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article
ISSN	2471-1888
ISSN (online)	2471-1888
DOI	10.3934/microbiol.2021003
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Article ; Online: Base Excision Repair AP-Endonucleases-Like Genes Modulate DNA Damage Response and Virulence of the Human Pathogen

Oliveira, Rayssa Karla de Medeiros / Hurtado, Fabián Andrés / Gomes, Pedro Henrique / Puglia, Luiza Lassi / Ferreira, Fernanda Fonsêca / Ranjan, Kunal / Albuquerque, Patrícia / Poças-Fonseca, Márcio José / Silva-Pereira, Ildinete / Fernandes, Larissa

Journal of fungi (Basel, Switzerland)

2021 Volume 7, Issue 2

Abstract: Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability ... ...

Abstract	Pathogenic microbes are exposed to a number of potential DNA-damaging stimuli during interaction with the host immune system. Microbial survival in this situation depends on a fine balance between the maintenance of DNA integrity and the adaptability provided by mutations. In this study, we investigated the association of the DNA repair response with the virulence of
Language	English
Publishing date	2021-02-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7020133
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Article ; Online: Intracellular Eukaryotic Pathogens' Virulence Attributes and Their Interplay with Host Immune Defenses.

Bocca, Anamélia Lorenzetti / de Almeida Soares, Célia Maria / Nosanchuk, Joshua D / Silva-Pereira, Ildinete

Mediators of inflammation

2017 Volume 2017, Page(s) 1264974

MeSH term(s)	Animals ; Eukaryota/immunology ; Eukaryota/virology ; Host-Pathogen Interactions/physiology ; Humans ; Immunosuppression ; Virulence/physiology
Language	English
Publishing date	2017-11-05
Publishing country	United States
Document type	Editorial
ZDB-ID	1137605-3
ISSN	1466-1861 ; 0962-9351
ISSN (online)	1466-1861
ISSN	0962-9351
DOI	10.1155/2017/1264974
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Zs.A 3575: Show issues

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Article ; Online: The role of Cryptococcus neoformans histone deacetylase genes in the response to antifungal drugs, epigenetic modulators and to photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion in vitro.

Journal of photochemistry and photobiology. B, Biology

2021 Volume 216, Page(s) 112131

Abstract	Cryptococcus is a globally distributed fungal pathogen that primarily afflicts immunocompromised individuals. The therapeutic options are limited and include mostly amphotericin B or fluconazole, alone or in combination. The extensive usage of antifungals allowed the selection of resistant pathogens posing threats to global public health. Histone deacetylase genes are involved in Cryptococcus virulence, and in pathogenicity and resistance to azoles in Candida albicans. Aiming to assess whether histone deacetylase genes are involved in antifungal response and in synergistic drug interactions, we evaluated the activity of amphotericin B, fluconazole, sulfamethoxazole, sodium butyrate or trichostatin A (histone deacetylase inhibitors), and hydralazine or 5- aza-2'-deoxycytidine (DNA methyl-transferase inhibitors) against different Cryptococcus neoformans strains, C. neoformans histone deacetylase null mutants and Cryptococcus gattii NIH198. The drugs were employed alone or in different combinations. Fungal growth after photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion, alone or in combination with the aforementioned drugs, was assessed for the C. neoformans HDAC null mutant strains. Our results showed that fluconazole was synergistic with sodium butyrate or with trichostatin A for the hda1Δ/hos2Δ double mutant strain. Sulfamethoxazole was synergistic with sodium butyrate or with hydralazine also for hda1Δ/hos2Δ. These results clearly indicate a link between HDAC impairment and drug sensitivity. Photodynamic therapy efficacy on controlling the growth of the HDAC mutant strains was increased by amphotericin B, fluconazole, sodium butyrate or hydralazine. This is the first study in Cryptococcus highlighting the combined effects of antifungal drugs, histone deacetylase or DNA methyltransferase inhibitors and photodynamic therapy in vitro.
MeSH term(s)	Amphotericin B/chemistry ; Antifungal Agents/metabolism ; Bacterial Proteins/genetics ; Butyric Acid/chemistry ; Cryptococcosis/drug therapy ; Cryptococcus neoformans/enzymology ; Drug Synergism ; Emulsions/chemistry ; Epigenesis, Genetic/drug effects ; Fluconazole/chemistry ; Gene Expression Regulation, Bacterial/drug effects ; Histone Deacetylases/genetics ; Humans ; Hydroxamic Acids/chemistry ; Indoles/metabolism ; Indoles/pharmacology ; Nanoparticles/chemistry ; Organometallic Compounds/metabolism ; Organometallic Compounds/pharmacology ; Photochemotherapy/methods ; Sulfamethoxazole/chemistry
Chemical Substances	Antifungal Agents ; Bacterial Proteins ; Emulsions ; Hydroxamic Acids ; Indoles ; Organometallic Compounds ; Butyric Acid (107-92-6) ; chloroaluminum phthalocyanine (14154-42-8) ; trichostatin A (3X2S926L3Z) ; Amphotericin B (7XU7A7DROE) ; Fluconazole (8VZV102JFY) ; Histone Deacetylases (EC 3.5.1.98) ; Sulfamethoxazole (JE42381TNV)
Language	English
Publishing date	2021-01-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	623022-2
ISSN	1873-2682 ; 1011-1344
ISSN (online)	1873-2682
ISSN	1011-1344
DOI	10.1016/j.jphotobiol.2021.112131
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2347: Show issues

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Article ; Online: Laccase Affects the Rate of Cryptococcus neoformans Nonlytic Exocytosis from Macrophages.

Frazão, Stefânia de Oliveira / Sousa, Herdson Renney de / Silva, Lenise Gonçalves da / Folha, Jéssica Dos Santos / Gorgonha, Kaio César de Melo / Oliveira, Getúlio Pereira de / Felipe, Maria Sueli Soares / Silva-Pereira, Ildinete / Casadevall, Arturo / Nicola, André Moraes / Albuquerque, Patrícia

mBio

2020 Volume 11, Issue 5

Abstract: Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction ... ...

Abstract	Nonlytic exocytosis is a process in which previously ingested microbes are expelled from host phagocytes with the concomitant survival of both cell types. This process has been observed in the interaction of
MeSH term(s)	Animals ; Brazil ; Cells, Cultured ; Cryptococcosis/immunology ; Cryptococcosis/microbiology ; Cryptococcus neoformans/enzymology ; Cryptococcus neoformans/genetics ; Cryptococcus neoformans/pathogenicity ; Exocytosis ; Humans ; Immunocompromised Host ; Laccase/analysis ; Laccase/biosynthesis ; Laccase/genetics ; Laccase/metabolism ; Macrophages/microbiology ; Melanins/metabolism ; Mice ; Mice, Inbred BALB C ; Virulence
Chemical Substances	Melanins ; Laccase (EC 1.10.3.2)
Language	English
Publishing date	2020-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.02085-20
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Article: Broth microdilution In Vitro screening: an easy and fast method to detect new antifungal compounds

de-Souza-Silva, Calliandra Maria / Guilhelmelli, Fernanda / Zamith-Miranda, Daniel / de Oliveira, Marco Antônio / Nosanchuk, Joshua Daniel / Silva-Pereira, Ildinete / Albuquerque, Patrícia

Journal of visualized experiments. 2018 Feb. 14, , no. 132

2018

Abstract: Fungal infections have become an important medical condition in the last decades, but the number of available antifungal drugs is limited. In this scenario, the search for new antifungal drugs is necessary. The protocol reported here details a method to ... ...

Abstract	Fungal infections have become an important medical condition in the last decades, but the number of available antifungal drugs is limited. In this scenario, the search for new antifungal drugs is necessary. The protocol reported here details a method to screen peptides for their antifungal properties. It is based on the broth microdilution susceptibility test from the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines with modifications to suit the research of antimicrobial peptides as potential new antifungals. This protocol describes a functional assay to evaluate the activity of antifungal compounds and may be easily modified to suit any particular class of molecules under investigation. Since the assays are performed in 96-well plates using small volumes, a large-scale screening can be completed in a short amount of time, especially if carried out in an automation setting. This procedure illustrates how a standardized and adjustable clinical protocol can help the bench-work pursuit of new molecules to improve the therapy of fungal diseases.
Keywords	antifungal agents ; antifungal properties ; antimicrobial peptides ; automation ; fungi ; guidelines ; minimum inhibitory concentration ; screening ; therapeutics
Language	English
Dates of publication	2018-0214
Size	p. e57127.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/57127
Database	NAL-Catalogue (AGRICOLA)

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