Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment

Arruda, Denise C.; Matsuo, Alisson L.; Silva, Luiz S.; Real, Fernando; Leitão, Natanael P.; Pires, Jhon H. S.; Caires, Antonio C. F.; Garcia, Daniel M.; Cunha, Fernanda F. M.; Puccia, Rosana; Longo, Larissa V. G.

doi:10.1128/aac.00512-15

Cited by 7 publications

(12 citation statements)

References 48 publications

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“…The defects of autophagy are associated with neurodegeneration, aging, metabolic syndrome, and inflammatory disorders. 25 The TEM results presented in this study revealed that the accumulation of autophagosomes was increased in corneas of patients with FK compared with healthy donors. Next, we established A. fumigatus keratitis models to further determine the expression of autophagy.…”

Section: Discussionmentioning

confidence: 48%

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Cui

Lin

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Li C, Li C, Lin J, et al. The role of autophagy in the innate immune response to fungal keratitis caused by Aspergillus fumigatus infection. Invest Ophthalmol Vis Sci. 2020;61(2):25. https://doi.org/10.1167/iovs.61.2.25 PURPOSE.To determine the role of autophagy in the innate immune response to fungal keratitis (FK) caused by Aspergillus fumigatus infection. METHODS.Corneal samples obtained from patients and mice with FK were visualized via transmission electron microscopy (TEM). Autophagy-related proteins LC3B-II, Beclin-1, LAMP-1, and p62 in A. fumigatus-infected corneas of C57BL/6 mice were tested by Western blot. After treatment with autophagy inhibitors 3-methyladenine (3-MA), chloroquine (CQ), or inducer rapamycin, autophagy-related proteins were detected by Western blot. Corneas were photographed with slit lamp microscopy and pathological changes were observed by hematoxylin and eosin staining. Polymorphonuclear neutrophilic leukocytes (PMNs) were assessed by immunofluorescent staining and observed under TEM. The levels of CXCL-1, IL-1β, HMGB1, IL-18, TNF-α, and IL-10 were tested by reverse transcription polymerase chain reaction and Western blot. The quantification of fungal loads was detected and photographed. RESULTS.The accumulation of autophagosomes in corneas of patients and mice with FK was observed with TEM. The expression of LC3B-II, Beclin-1, and LAMP-1 was elevated in corneas after fungal infection, whereas p62 was reduced. Treatment with 3-MA or CQ upregulated clinical scores, pathological changes, and the expression of CXCL-1, IL-1β, HMGB1, IL-18, and TNF-α except IL-10. The morphology of PMNs was changed and PMN recruitment was increased in mice corneas treated with 3-MA or CQ, whereas rapamycin reduced the inflammatory response to keratitis. These results were statistically significant. CONCLUSIONS. A. fumigatus infection increases the expression of autophagy in corneas.Autophagy plays an anti-inflammatory role in the innate immune response to A. fumigatus keratitis.

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Section: Discussionmentioning

confidence: 48%

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Cui

Lin

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…A role for the P. anserina cyclophilin D ortholog in RCD 343 344 345 as well as for autophagy in aging and lifespan control of P. anserina 346 347 have been reported. Further instances of fungal RCD 306 348 have been documented in Paracoccidioides brasiliensis 349 , Colletotrichum gloeosporioides 350 , Fusarium oxysporum 351 , Fusarium graminearum 352 , Mucor racemosus 353 , Botrytis cinerea 354 , Penicillium expansum 355 , Rhizopus oryzae 356 , Scedosporium prolificans 357 and Neurospora crassa 358 . As multicellular organisms, filamentous fungi have developed programs that are reminiscent of organismal RCD.…”

Section: Rcd In Other Yeasts and Filamentous Fungimentioning

confidence: 99%

Guidelines and recommendations on yeast cell death nomenclature

Carmona-Gutiérrez¹,

Bauer²,

Zimmermann³

et al. 2018

Microb Cell

163

154

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Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.

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“…In P . brasiliensis , apoptosis and autophagy-like mechanisms have recently been implicated in a cyclopalladated 7a-mediated cell death [ 32 ]. Gontijo et al [ 33 ] showed that 21 of 34 autophagy-related genes described in Saccharomyces cerevisiae are present in a basidiomycete, Cryptococcus neoformans , and in Candida albicans and Aspergillus fumigatus , both ascomycetes.…”

Section: Introductionmentioning

confidence: 99%

“…Studies about the mechanisms responsible for triggering autophagy in Paracoccidioides spp , as well as the occurrence of the autophagic process itself, have only been initiated very recently with a single demonstration made by Arruda et al [ 32 ] that mechanisms resembling autophagy-like cell death may be behind the cyclopalladated 7a compound killing of P . brasiliensis .…”

Section: Introductionmentioning

confidence: 99%

Autophagy in Paracoccidioides brasiliensis under normal mycelia to yeast transition and under selective nutrient deprivation

et al. 2018

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Paracoccidioides spp. is a thermally dimorphic fungus endemic to Latin America and the etiological agent of paracoccidioidomycosis (PCM), a granulomatous disease acquired through fungal propagule inhalation by its mammalian host. The infection is established after successful mycelia to yeast transition in the host pulmonary alveoli. The challenging environment inside the host exposes the fungus to the need of adaptation in order to circumvent nutritional, thermal, oxidative, immunological and other stresses that can directly affect their survival. Considering that autophagy is a response to abrupt environmental changes and is induced by stress conditions, this study hypothesizes that this process might be crucially involved in the adaptation of Paracoccidioides spp. to the host and, therefore, it is essential for the proper establishment of the disease. By labelling autophagous vesicles with monodansylcadaverine, autophagy was observed as an early event in cells during the normal mycelium to yeast transition, as well as in yeast cells of P. brasiliensis under glucose deprivation, and under either rapamycin or 3-methyladenine (3-MA). Findings in this study demonstrated that autophagy is triggered in P. brasiliensis during the thermal-induced mycelium to yeast transition and by glucose-limited conditions in yeasts, both of which modulated by rapamycin or 3-MA. Certainly, further genetic and in vivo analyses are needed in order to finally address the contribution of autophagy for adaptation. Yet, our data propose that autophagy possibly plays an important role in Paracoccidioides brasiliensis virulence and pathogenicity.

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Cyclopalladated Compound 7a Induces Apoptosis- and Autophagy-Like Mechanisms in Paracoccidioides and Is a Candidate for Paracoccidioidomycosis Treatment

Cited by 7 publications

References 48 publications

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

The Role of Autophagy in the Innate Immune Response to Fungal Keratitis Caused by Aspergillus fumigatus Infection

Guidelines and recommendations on yeast cell death nomenclature

Autophagy in Paracoccidioides brasiliensis under normal mycelia to yeast transition and under selective nutrient deprivation

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