Ramos-Sevillano, E;
Urzainqui, A;
Campuzano, S;
Moscoso, M;
Gonzalez-Camacho, F;
Domenech, M;
Rodriguez de Cordoba, S;
... Yuste, J; + view all
(2015)
Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response.
Infection and Immunity
, 83
(2)
pp. 591-603.
10.1128/IAI.02811-14.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1128/IAI.02811-14 |
| Publisher version: | http://dx.doi.org/10.1128/IAI.02811-14 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Immunology, Infectious Diseases, GENES-ENCODING PNEUMOLYSIN, COMPLEMENT EVASION, CAPSULAR POLYSACCHARIDE, TOXIN PNEUMOLYSIN, VIRULENCE FACTORS, HUMAN NEUTROPHILS, BIOFILM FORMATION, STRUCTURAL BASIS, FACTOR-H, 2 PARTS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1457319 |
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