O-Glycosylation in Cell Wall Proteins in Scedosporium prolificans Is Critical for Phagocytosis and Inflammatory Cytokines Production by Macrophages

Xisto, Mariana Ingrid Dutra da Silva; Bittencourt, Vera Carolina B.; Liporagi-Lopes, Livia Cristina; Haido, Rosa Maria Tavares; Mendonça, Morena Scopel Amorim; Sassaki, Guilherme L.; Figueiredo, Rodrigo T.; Romanos, Maria Teresa V.; Barreto‐Bergter, Eliana

doi:10.1371/journal.pone.0123189

Cited by 26 publications

(39 citation statements)

References 46 publications

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“… 9 The filamentous fungus L. prolificans (formerly Scedosporium prolificans ) can interact with peritoneal macrophages, and its surface PRM also participates in this crucial event. 23 Similarly, in A. fumigatus , it was reported that a small number of conidia were internalised and that most of them remained adhered to the external surface of the A549 cells. Those adhered conidia could externally germinate, generating long hyphae after 24 h of fungi-host cell contact.…”

Section: Resultsmentioning

confidence: 95%

Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells

Aor

Mello

Sangenito

et al. 2018

Mem. Inst. Oswaldo Cruz

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BACKGROUND Scedosporium apiospermum is a ubiquitous, emerging and multidrug-resistant fungal pathogen with still rather unknown virulence mechanisms.OBJECTIVES/METHODS The cellular basis of the in vitro interaction between fungi and host cells/tissues is the determinant factor for the development of a successful in vivo infection. Herein, we evaluated the interaction of S. apiospermum conidia with lung epithelial (A549), lung fibroblast (MRC-5) and RAW 264.7 macrophages by light and scanning/transmission electron microscopy.FINDINGS After 4 h of fungi-host cell contact, the percentage of infected mammalian cells and the number of fungi per infected cell was measured by light microscopy, and the following association indexes were calculated for A549, MRC-5 and macrophage cells: 73.2 ± 25.9, 69.7 ± 22.5 and 59.7 ± 11.1, respectively. Both conidia and germinated conidia were regularly observed interacting with the evaluated cells, with a higher prevalence of non-germinated conidia. Interestingly, nests of germinated conidia were evidenced at the surface of lung cells by scanning electron microscopy. Some germination projections and hyphae were seen penetrating/evading the mammalian cells. Furthermore, internalised conidia were seen within vacuoles as visualised by transmission electron microscopy.MAIN CONCLUSIONS The present study contributes to a better understanding of S. apiospermum pathogenesis by demonstrating the first steps of the infection process of this opportunistic fungus.

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Section: Resultsmentioning

confidence: 95%

Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells

Aor

Mello

Sangenito

et al. 2018

Mem. Inst. Oswaldo Cruz

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“…Furthermore, those authors described that after 2 h of coculturing of S. boydii and HEp2 cells, the conidia started to germinate and, subsequently, to penetrate into the plasma membrane of epithelial cells [11]. The PRMs also mediate the in vitro adhesion between L. prolificans conidia and mouse peritoneal macrophages [16]. The conidial adhesion followed by its germination was also observed during the in vitro interaction events of S. apiospermum, S. boydii, and S. aurantiacum with lung epithelial cells (A549), lung fibroblasts (MRC-5), and mouse macrophages (RAW 264.7 line) [7,14,19,20].…”

Section: Resultsmentioning

confidence: 99%

“…For filamentous fungi, some features are well known for the establishment of a successfully infectious process, such as cell wall composition, conidial germination, and secretion of metabolites and hydrolytic enzymes [8,9]. Some of those fungal structures have been studied on Scedosporium/Lomentospora species, such as (i) surface molecules (e.g., peptidorhamnomannans, glucosylceramides, and α-glucan) capable of interacting with host receptors as well as modulating the host immunity responses, (ii) proteases able to cleave key host proteins, including antimicrobial peptides, extracellular matrix proteins, and humoral immune components, (iii) high capacity of conidia to germinate under diverse environmental conditions, and (iv) biofilm formation on a variety of abiotic surfaces and also over mammalian cells [7,8,[10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Insights into the interaction of Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum, and Lomentospora prolificans with lung epithelial cells

et al. 2019

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Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/ Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.

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“…In the context of fungal molecules that could influence bacterial growth, the present work studied peptidorhamnomannans (PRMs), glycoconjugates commonly exposed on Scedosporium and Lomentospora cell wall that play important roles in cell adhesion and interaction with host immune system, leading to the release of inflammatory cytokines by phagocytic cells (Lopes et al, 2011). PRMs have been already described and characterized in Scedosporium boydii, Scedosporium apiospermum, and Lomentospora prolificans (Pinto et al, 2001;Lopes et al, 2010;Xisto et al, 2015), as well as in Scedosporium aurantiacum (de Meirelles et al, 2020). The PRMs of these four species possess similar epitopes as well as distinct species-specific oligosaccharide chains.…”

Section: Introductionmentioning

confidence: 99%

Peptidorhamnomannans From Scedosporium and Lomentospora Species Display Microbicidal Activity Against Bacteria Commonly Present in Cystic Fibrosis Patients

Oliveira

Xisto

Rollin-Pinheiro

et al. 2020

Front. Cell. Infect. Microbiol.

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Scedosporium and Lomentospora species are filamentous fungi that cause a wide range of infections in humans. They are usually found in the lungs of cystic fibrosis (CF) patients and are the second most frequent fungal genus after Aspergillus species. Several studies have been recently performed in order to understand how fungi and bacteria interact in CF lungs, since both can be isolated simultaneously from patients. In this context, many bacterial molecules were shown to inhibit fungal growth, but little is known about how fungi could interfere in bacterial development in CF lungs. Scedosporium and Lomentospora species present peptidorhamnomannans (PRMs) in their cell wall that play crucial roles in fungal adhesion and interaction with host epithelial cells and the immune system. The present study aimed to analyze whether PRMs extracted from Lomentospora prolificans, Scedosporium apiospermum, Scedosporium boydii, and Scedosporium aurantiacum block bacterial growth and biofilm formation in vitro. PRM from L. prolificans and S. boydii displayed the best bactericidal effect against methicillin resistant Staphylococcus aureus (MRSA), Burkholderia cepacia, and Escherichia coli, but not Pseudomonas aeruginosa, all of which are the most frequently found bacteria in CF lungs. In addition, biofilm formation was inhibited in all bacteria tested using PRMs at minimal inhibitory concentration (MIC). These results suggest that PRMs from the Scedosporium and Lomentospora surface seem to play an important role in Scedosporium colonization in CF patients, helping to clarify how these pathogens interact to each other in CF lungs.

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O-Glycosylation in Cell Wall Proteins in Scedosporium prolificans Is Critical for Phagocytosis and Inflammatory Cytokines Production by Macrophages

Cited by 26 publications

References 46 publications

Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells

Ultrastructural viewpoints on the interaction events of Scedosporium apiospermum conidia with lung and macrophage cells

Insights into the interaction of Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum, and Lomentospora prolificans with lung epithelial cells

Peptidorhamnomannans From Scedosporium and Lomentospora Species Display Microbicidal Activity Against Bacteria Commonly Present in Cystic Fibrosis Patients

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