Identification of the Bartonella autotransporter CFA as a protective antigen and hypervariable target of neutralizing antibodies in mice
Year: 2022
Type: article
Abstract: Summary 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.
Institution: University of Basel
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G2440410302, Memory B cell immunity in chronic viral infection, NCCR AntiResist: New approaches to combat antibiotic-resistant bacteria, G3912525606, Immunity and tolerance in persistent viral infection, G6023213073, Bacterial Type IV Secretion (T4S): Cellular, Molecular, and Evolutionary Basis of the Subversion of Host Cell Functions by Translocated Effector Proteins, G8690818240
OpenAlex ID: W4283026028