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.
Author Summary The incidence of fungal infections has increased dramatically over the last 50 years, largely because of the increasing size of the population at risk, which especially includes immunocompromised hosts. Scedosporium apiospermum is a filamentous fungus that causes a variety of infections, ranging from localized disease to life-threatening disseminated infections. Glycoproteins are molecules present in the fungal surface and are comprised of carbohydrate and protein components. They are involved in different important functions in the fungal cell. Monoclonal antibodies can be used as therapeutic agents for infectious disease, but some factors involved in their efficacy are often not well understood. We found that monoclonal antibodies to glycoproteins present in fungal surface can be nonprotective and can even enhance the disease. The administration of these antibodies can affect functions of the fungal cell and the immune cells, resulting in a survival advantage for the fungus during interactions with the host.