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Monoclonal antibodies against peptidorhamnomannans of Scedosporium apiospermum enhance the pathogenicity of the fungus.

Lopes LC, Rollin-Pinheiro R, Guimarães AJ, Bittencourt VC, Martinez LR, Koba W, Farias SE, Nosanchuk JD, Barreto-Bergter E - PLoS Negl Trop Dis (2010)

Bottom Line: In the present study, three monoclonal antibodies (mAbs, IgG1) to S. apiospermum derived PRM were generated and their effects on S. apiospermum were examined in vitro and in vivo.In culture, addition of the PRM mAbs increased S. apiospermum conidia germination and reduced conidial phagocytosis by J774.16 macrophages.Further insights into the effects of these glycopeptides on the pathobiology of S. apiospermum may lead to new avenues for preventing and treating scedosporiosis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT
Scedosporium apiospermum is part of the Pseudallescheria-Scedosporium complex. Peptidorhamnomannans (PRMs) are cell wall glycopeptides present in some fungi, and their structures have been characterized in S. apiospermum, S. prolificans and Sporothrix schenckii. Prior work shows that PRMs can interact with host cells and that the glycopeptides are antigenic. In the present study, three monoclonal antibodies (mAbs, IgG1) to S. apiospermum derived PRM were generated and their effects on S. apiospermum were examined in vitro and in vivo. The mAbs recognized a carbohydrate epitope on PRM. In culture, addition of the PRM mAbs increased S. apiospermum conidia germination and reduced conidial phagocytosis by J774.16 macrophages. In a murine infection model, mice treated with antibodies to PRM died prior to control animals. Thus, PRM is involved in morphogenesis and the binding of this glycopeptide by mAbs enhanced the virulence of the fungus. Further insights into the effects of these glycopeptides on the pathobiology of S. apiospermum may lead to new avenues for preventing and treating scedosporiosis.

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Related in: MedlinePlus

Phagolysosomal fusion with S. apiospermum.Localization of S. apiospermum conidia in phagolysosomes. MAb F10 increased the phagolysosomal fusion in J774.16 cells (A). Immunofluorescence analysis of phagolysosomal fusion in J774.16 macrophages by FITC-dextran colocalization with NHS-Rho-labeled S. apiospermum conidia. S. apiospermum conidia (red) previously incubated with mAb F10 (B), C7 (C), C11 (D) and irrelevant control mAb (E) with a J774.16 cell with FITC-dextran (green). Growth of S. apiospermum conidia in neutral and acidic medium (DMEM) for four h (F) (* P<0.05). Both experiments were performed three times. Scale bar: 50 µm.
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pntd-0000853-g004: Phagolysosomal fusion with S. apiospermum.Localization of S. apiospermum conidia in phagolysosomes. MAb F10 increased the phagolysosomal fusion in J774.16 cells (A). Immunofluorescence analysis of phagolysosomal fusion in J774.16 macrophages by FITC-dextran colocalization with NHS-Rho-labeled S. apiospermum conidia. S. apiospermum conidia (red) previously incubated with mAb F10 (B), C7 (C), C11 (D) and irrelevant control mAb (E) with a J774.16 cell with FITC-dextran (green). Growth of S. apiospermum conidia in neutral and acidic medium (DMEM) for four h (F) (* P<0.05). Both experiments were performed three times. Scale bar: 50 µm.

Mentions: Fusion of lysosomes with phagosomes was observed by the detection of FITC-dextran with S. apiospermum conidia within macrophages. The majority of phagosomes containing S. apiospermum opsonized with mAb F10 demonstrated co-localization of FITC-dextran with NHSRho-labeled conidia (Figure 4A and B), which was significantly increased compared to the other conditions examined, including mAb C7 (Figure 4A and C), mAb C11 (Figure 4A and D) and irrelevant control mAb (Figure 4A and E). In order to evaluate the capacity of S. apiospermum conidia to germinate and survive in acidic media, cells were incubated in DMEM at pH 7.2 or pH 4.0. Interestingly, there was a significant increase (127%) in the number of germinated conidia at pH 4.0,compared to pH 7.2 (Figure 4F).


Monoclonal antibodies against peptidorhamnomannans of Scedosporium apiospermum enhance the pathogenicity of the fungus.

Lopes LC, Rollin-Pinheiro R, Guimarães AJ, Bittencourt VC, Martinez LR, Koba W, Farias SE, Nosanchuk JD, Barreto-Bergter E - PLoS Negl Trop Dis (2010)

Phagolysosomal fusion with S. apiospermum.Localization of S. apiospermum conidia in phagolysosomes. MAb F10 increased the phagolysosomal fusion in J774.16 cells (A). Immunofluorescence analysis of phagolysosomal fusion in J774.16 macrophages by FITC-dextran colocalization with NHS-Rho-labeled S. apiospermum conidia. S. apiospermum conidia (red) previously incubated with mAb F10 (B), C7 (C), C11 (D) and irrelevant control mAb (E) with a J774.16 cell with FITC-dextran (green). Growth of S. apiospermum conidia in neutral and acidic medium (DMEM) for four h (F) (* P<0.05). Both experiments were performed three times. Scale bar: 50 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957425&req=5

pntd-0000853-g004: Phagolysosomal fusion with S. apiospermum.Localization of S. apiospermum conidia in phagolysosomes. MAb F10 increased the phagolysosomal fusion in J774.16 cells (A). Immunofluorescence analysis of phagolysosomal fusion in J774.16 macrophages by FITC-dextran colocalization with NHS-Rho-labeled S. apiospermum conidia. S. apiospermum conidia (red) previously incubated with mAb F10 (B), C7 (C), C11 (D) and irrelevant control mAb (E) with a J774.16 cell with FITC-dextran (green). Growth of S. apiospermum conidia in neutral and acidic medium (DMEM) for four h (F) (* P<0.05). Both experiments were performed three times. Scale bar: 50 µm.
Mentions: Fusion of lysosomes with phagosomes was observed by the detection of FITC-dextran with S. apiospermum conidia within macrophages. The majority of phagosomes containing S. apiospermum opsonized with mAb F10 demonstrated co-localization of FITC-dextran with NHSRho-labeled conidia (Figure 4A and B), which was significantly increased compared to the other conditions examined, including mAb C7 (Figure 4A and C), mAb C11 (Figure 4A and D) and irrelevant control mAb (Figure 4A and E). In order to evaluate the capacity of S. apiospermum conidia to germinate and survive in acidic media, cells were incubated in DMEM at pH 7.2 or pH 4.0. Interestingly, there was a significant increase (127%) in the number of germinated conidia at pH 4.0,compared to pH 7.2 (Figure 4F).

Bottom Line: In the present study, three monoclonal antibodies (mAbs, IgG1) to S. apiospermum derived PRM were generated and their effects on S. apiospermum were examined in vitro and in vivo.In culture, addition of the PRM mAbs increased S. apiospermum conidia germination and reduced conidial phagocytosis by J774.16 macrophages.Further insights into the effects of these glycopeptides on the pathobiology of S. apiospermum may lead to new avenues for preventing and treating scedosporiosis.

View Article: PubMed Central - PubMed

Affiliation: Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.

ABSTRACT
Scedosporium apiospermum is part of the Pseudallescheria-Scedosporium complex. Peptidorhamnomannans (PRMs) are cell wall glycopeptides present in some fungi, and their structures have been characterized in S. apiospermum, S. prolificans and Sporothrix schenckii. Prior work shows that PRMs can interact with host cells and that the glycopeptides are antigenic. In the present study, three monoclonal antibodies (mAbs, IgG1) to S. apiospermum derived PRM were generated and their effects on S. apiospermum were examined in vitro and in vivo. The mAbs recognized a carbohydrate epitope on PRM. In culture, addition of the PRM mAbs increased S. apiospermum conidia germination and reduced conidial phagocytosis by J774.16 macrophages. In a murine infection model, mice treated with antibodies to PRM died prior to control animals. Thus, PRM is involved in morphogenesis and the binding of this glycopeptide by mAbs enhanced the virulence of the fungus. Further insights into the effects of these glycopeptides on the pathobiology of S. apiospermum may lead to new avenues for preventing and treating scedosporiosis.

Show MeSH
Related in: MedlinePlus