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Título

Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response

AutorRamos-Sevillano, Elisa ; Moscoso, Miriam ; Domenech, Mirian ; Rodríguez de Córdoba, Santiago ; García, Ernesto
Fecha de publicaciónfeb-2015
EditorAmerican Society for Microbiology
CitaciónInfection and Immunity, February 2015 Volume 83 Number 2
ResumenThe complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.
Descripción39 p.-8 fig. Ramos-Sevillano, Elisa et alt.
Versión del editorhttp://dx.doi.org/10.1128/IAI.02811-14
URIhttp://hdl.handle.net/10261/108351
DOI10.1128/IAI.02811-14
ISSN0019-9567
E-ISSN1098-5522
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