Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen


Hart, PJ; O'Shaughnessy, CM; Siggins, MK; Bobat, S; Kingsley, RA; Goulding, DA; Crump, JA; Reyburn, H; Micoli, F; Dougan, G; Cunningham, AF; MacLennan, CA; (2016) Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen. Plos One, 11 (1). ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0145945

[img] Text - Published Version
License:

Download (2MB)

Abstract

Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement-and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement-and phagocyte-mediated modalities of antibodydependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies.

Item Type: Article
Keywords: INVASIVE NONTYPHOIDAL SALMONELLA, SERUM RESISTANCE, POLYSACCHARIDE, COMPLEMENT, MUTANTS, CELLS, EXPRESSION, PROTECTION, RESPONSES, CHILDREN
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
PubMed ID: 26741681
Web of Science ID: 367810600014
URI: http://researchonline.lshtm.ac.uk/id/eprint/2534165

Statistics


Download activity - last 12 months
Downloads since deposit
50Downloads
57Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item