UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response

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. Green open access

[img]
Preview
Text
Brown_Infect. Immun.-2015-Ramos-Sevillano-591-603.pdf - Published version

Download (2MB) | Preview

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
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
Downloads since deposit
59Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item