Immunoglobulin Attenuates Streptokinase-Mediated Virulence in Streptococcus dysgalactiae Subspecies equisimilis Necrotizing Fasciitis
| Autor: | Annelies S. Zinkernagel, Andrew Hollands, Nadia Keller, Reto A. Schuepbach, Ewerton Marques Maggio, Federica Andreoni, Victor Nizet, Andrina Neff, Fabio Ugolini |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Pathogenesis and Host Response bacterial spreading pooled human immunoglobulin medicine.drug_class Virulence Factors necrotizing fasciitis Streptokinase medicine.medical_treatment Antibiotics Virulence medicine.disease_cause Microbiology 03 medical and health sciences Major Articles and Brief Reports Fibrinolytic Agents Streptococcal Infections Fibrinolysis Blocking antibody medicine Immunology and Allergy Animals Humans streptokinase Fasciitis Necrotizing Fasciitis Pathogen Streptococcus dysgalactiae subspeciesequisimilis Streptococcus business.industry medicine.disease Antibodies Bacterial 3. Good health Mice Inbred C57BL 030104 developmental biology Infectious Diseases Host-Pathogen Interactions Female fibrinolysis business medicine.drug |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 |
| Popis: | A clinicalStreptococcus dysgalactiae equisimilis strain secreting high levels of streptokinase promoted severe disease in a patient lacking anti-streptokinase antibodies. Exogenous immunoglobulins efficiently blocked streptokinase-mediated fibrinolysis in vitro and attenuated streptokinase-mediated virulence in a necrotizing fasciitis mouse model. Background Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated withStreptococcus dysgalactiae subspeciesequisimilis (SDSE). Methods We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs. |
| Databáze: | OpenAIRE |
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