2024-03-28T08:50:50Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/74462022-09-29T11:43:31Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Uria, Maria J
author
Zhang, Qian
author
Li, Yanwen
author
Chan, Angel
author
Exley, Rachel M.
author
Gollan, Bridget
author
Chan, Hannah
author
Feavers, Ian
author
Yarwood, Andy
author
Abad, Raquel
author
Borrow, Ray
author
Fleck, Roland A.
author
Mulloy, Barbara
author
Vazquez-Moreno, Julio Alberto
author
Tang, Christoph M.
author
2008-06
The presence of serum bactericidal antibodies is a proven correlate of protection against systemic infection with the important human pathogen Neisseria meningitidis. We have identified three serogroup C N. meningitidis (MenC) isolates recovered from patients with invasive meningococcal disease that resist killing by bactericidal antibodies induced by the MenC conjugate vaccine. None of the patients had received the vaccine, which has been successfully introduced in countries in North America and Europe. The increased resistance was not caused by changes either in lipopolysaccharide sialylation or acetylation of the alpha2-9-linked polysialic acid capsule. Instead, the resistance of the isolates resulted from the presence of an insertion sequence, IS1301, in the intergenic region (IGR) between the sia and ctr operons, which are necessary for capsule biosynthesis and export, respectively. The insertion sequence led to an increase in the transcript levels of surrounding genes and the amount of capsule expressed by the strains. The increased amount of capsule was associated with down-regulation of the alternative pathway of complement activation, providing a generic mechanism by which the bacterium protects itself against bactericidal antibodies. The strains with IS1301 in the IGR avoided complement-mediated lysis in the presence of bactericidal antibodies directed at the outer membrane protein, PorA, or raised against whole cells.
J Exp Med. 2008 Jun 9;205(6):1423-34.
0022-1007
http://hdl.handle.net/20.500.12105/7446
18504306
10.1084/jem.20072577
1540-9538
The Journal of Experimental Medicine
A generic mechanism inNeisseria meningitidisfor enhanced resistance against bactericidal antibodies