期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 39, 页码 19659-19664出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1911922116
关键词
transposon mutagenesis; lipopolysaccharide; O antigen; Weil-Felix reaction; polysaccharide synthesis operon
资金
- University of Chicago
- National Institutes of Health [AI144136]
Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against Proteus vulgaris (Weil-Felix reaction). Although Weil-Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. Here, we developed a transposon for insertional mutagenesis of Rickettsia conorii, isolating variants defective for replication in cultured cells and in spotted fever pathogenesis. Mutations in the polysaccharide synthesis operon (pso) abolish lipopolysaccharide O-antigen synthesis and Weil-Felix serology and alter outer-membrane protein assembly. Unlike wild-type R. conorii, pso mutants cannot elicit bactericidal antibodies that bind O antigen. The pso operon is conserved among rickettsial pathogens, suggesting that bactericidal antibodies targeting O antigen may generate universal immunity that could be exploited to develop vaccines against rickettsial diseases.
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