2026-06-14T03:37:35Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/85922025-05-07T10:55:31Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16980
Repisalud
author
Ramos-Sevillano, Elisa
author
Urzainqui, Ana
author
Campuzano, Susana
author
Moscoso, Miriam
author
Gonzalez-Camacho, Fernando
author
Domenech Lucas, Mirian
author
Rodriguez de Cordoba, Santiago
author
Sánchez Madrid, Francisco
author
Brown, Jeremy S
author
García, Ernesto
author
Yuste, Jose Enrique
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
2019-11-14T11:13:51Z
2019-11-14T11:13:51Z
2015-02
Infect Immun. 2015 Feb;83(2):591-603. doi: 10.1128/IAI.02811-14. Epub 2014 Nov 17.
10.1128/IAI.02811-14
1098-5522
0019-9567
Infection and immunity
25404032
http://hdl.handle.net/20.500.12105/8592
The 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.
eng
Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
research article
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URL
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File
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application/pdf
PleiotropicEffectsOfCell_2015.pdf
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File
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text/plain
PleiotropicEffectsOfCell_2015.pdf.txt