Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response
Entity
UAM. Departamento de MedicinaPublisher
American Society for MicrobiologyDate
2015-01-01Citation
10.1128/IAI.02811-14
Infection and Immunity 83.2 (2015): 591-603
ISSN
0019-9567 (print); 1098-5522 (online)DOI
10.1128/IAI.02811-14Funded by
This work was supported by grant SAF2012-39444-C01/02 from MINECO. The Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) are initiatives of ISCIII. E.R.-S. was supported by an FPU fellowship from MINECOProject
Comunidad de Madrid. S2010/BMD-2332/INDISNETSubjects
bacterial cell wall; immune response; pathogenesis; pleiotropy; Streptococcus pneumoniae; MedicinaRights
© 2015, American Society for MicrobiologyAbstract
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
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Google Scholar:Ramos-Sevillano, Elisa
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Urzainqui, Ana
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Campuzano, Susana
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Moscoso, Miriam
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González-Camacho, Fernando
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Domenech, Mirian
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Rodríguez de Córdoba, Santiago
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Sánchez Madrid, Francisco
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Brown, Jeremy S.
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García, Ernesto
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Yusteb, Jose
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