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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

Effect of mAbs to PRM on the growth of S. apiospermum conidia.Viability of S. apiospermum in the presence of mAbs against PRM was accessed by MTT assay (A). Effect of mAbs against PRM on S. apiospermum morphogenesis (B–F). Percentage of cells producing germ tubes after 4 h (B). Morphology of S. apiospermum cells assessed by light microscopy after incubation with an irrelevant antibody (C) and with mAbs F10 (D), C7 (E), C11 (F). There is a stimulus in the germination, when mAbs are present (B–F). Bars in the panels represent standard errors and * P<0.05. Scale bar: 100µm. All the experiments were performed three times.
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pntd-0000853-g005: Effect of mAbs to PRM on the growth of S. apiospermum conidia.Viability of S. apiospermum in the presence of mAbs against PRM was accessed by MTT assay (A). Effect of mAbs against PRM on S. apiospermum morphogenesis (B–F). Percentage of cells producing germ tubes after 4 h (B). Morphology of S. apiospermum cells assessed by light microscopy after incubation with an irrelevant antibody (C) and with mAbs F10 (D), C7 (E), C11 (F). There is a stimulus in the germination, when mAbs are present (B–F). Bars in the panels represent standard errors and * P<0.05. Scale bar: 100µm. All the experiments were performed three times.

Mentions: The metabolic activity in S. apiospermum conidia in the presence of the three mAbs against PRM was examined by MTT reduction assay at 1, 2, 3, 4, 5, 6 and 20 h (Figure 5A). The greatest increase in activity was at 6 h, where the increase was 48%, 49% and 51% for F10, C7 and C11, respectively, in comparison with controls. There were no differences at 20 h (p>0.05), which is consistent with the germination of all viable conidia in medium alone by this time.


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)

Effect of mAbs to PRM on the growth of S. apiospermum conidia.Viability of S. apiospermum in the presence of mAbs against PRM was accessed by MTT assay (A). Effect of mAbs against PRM on S. apiospermum morphogenesis (B–F). Percentage of cells producing germ tubes after 4 h (B). Morphology of S. apiospermum cells assessed by light microscopy after incubation with an irrelevant antibody (C) and with mAbs F10 (D), C7 (E), C11 (F). There is a stimulus in the germination, when mAbs are present (B–F). Bars in the panels represent standard errors and * P<0.05. Scale bar: 100µm. All the experiments were performed three times.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000853-g005: Effect of mAbs to PRM on the growth of S. apiospermum conidia.Viability of S. apiospermum in the presence of mAbs against PRM was accessed by MTT assay (A). Effect of mAbs against PRM on S. apiospermum morphogenesis (B–F). Percentage of cells producing germ tubes after 4 h (B). Morphology of S. apiospermum cells assessed by light microscopy after incubation with an irrelevant antibody (C) and with mAbs F10 (D), C7 (E), C11 (F). There is a stimulus in the germination, when mAbs are present (B–F). Bars in the panels represent standard errors and * P<0.05. Scale bar: 100µm. All the experiments were performed three times.
Mentions: The metabolic activity in S. apiospermum conidia in the presence of the three mAbs against PRM was examined by MTT reduction assay at 1, 2, 3, 4, 5, 6 and 20 h (Figure 5A). The greatest increase in activity was at 6 h, where the increase was 48%, 49% and 51% for F10, C7 and C11, respectively, in comparison with controls. There were no differences at 20 h (p>0.05), which is consistent with the germination of all viable conidia in medium alone by this time.

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