Proteomics

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The Bartonella autotransporter CFA is a protective antigen and hypervariable target of neutralizing antibodies blocking erythrocyte infection


ABSTRACT: Antibodies are key to the clearance of Bartonella bacteremia, but the mechanisms and targets of protective antibodies are unknown and bacterial evasion strategies remain elusive. We studied experimental Bartonella taylorii infection of mice, its natural host, and investigated protective immune responses. Clearance of bacteremia depended on specific antibodies that interfere with bacterial attachment to erythrocytes. Accordingly, antibodies were effective in the absence of complement and Fc-receptors. Moreover, they formed independently of B-cell hypermutation and isotype class switch. The cloning of neutralizing monoclonal antibodies (mAbs) led to the identification of the bacterial autotransporter CFA as a protective antibody target, and vaccination against CFA protected against Bartonella bacteremia. MAb binding mapped to a region of CFA that is hypervariable in both human- and mouse-pathogenic Bartonella strains, suggesting mutational antibody evasion. These insights further our understanding of Bartonella immunity and immune evasion and elucidate mechanisms driving high Bartonella prevalence in the wild.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Bartonella Henselae

SUBMITTER: Alexander Schmidt  

LAB HEAD: Alexander Schmidt

PROVIDER: PXD028783 | Pride | 2022-08-12

REPOSITORIES: Pride

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Publications

Identification of the <i>Bartonella</i> autotransporter CFA as a protective antigen and hypervariable target of neutralizing antibodies in mice.

Siewert Lena K LK   Korotaev Aleksandr A   Sedzicki Jaroslaw J   Fromm Katja K   Pinschewer Daniel D DD   Dehio Christoph C  

Proceedings of the National Academy of Sciences of the United States of America 20220617 25


The bacterial genus <i>Bartonella</i> comprises numerous emerging pathogens that cause a broad spectrum of disease manifestations in humans. The targets and mechanisms of the anti-<i>Bartonella</i> immune defense are ill-defined and bacterial immune evasion strategies remain elusive. We found that experimentally infected mice resolved <i>Bartonella</i> infection by mounting antibody responses that neutralized the bacteria, preventing their attachment to erythrocytes and suppressing bacteremia in  ...[more]

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