Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation.
Cell Microbiol
; 21(10): e13085, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31290210
ABSTRACT
Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc- mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Edema Pulmonar
/
Síndrome de Dificultad Respiratoria
/
Infecciones Estafilocócicas
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Staphylococcus aureus
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Proteínas Bacterianas
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Proteínas del Sistema Complemento
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Fosfoinositido Fosfolipasa C
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Taiwán