Monoclonal antibodies against peptidorhamnomannans of Scedosporium apiospermum enhance the pathogenicity of the fungus.
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.
Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Livia C L
LC
Lopes
Rodrigo
R
Rollin-Pinheiro
Allan J
AJ
Guimarães
Vera C B
VC
Bittencourt
Luis R
LR
Martinez
Wade
W
Koba
Sandra E
SE
Farias
Joshua D
JD
Nosanchuk
Eliana
E
Barreto-Bergter
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009181:Mycoses / Q000276:immunology / Q000382:microbiology* / Q000401:mortality*; D010587:Phagocytosis; D021681:Scedosporium / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D016019:Survival Analysis
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; C107788:peptido-rhamnomannan