Author ORCID Identifier
https://orcid.org/0000-0001-6060-6918
Defense Date
2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Microbiology & Immunology
First Advisor
Jason Carlyon
Second Advisor
Richard Marconi
Third Advisor
Daniel Miller
Fourth Advisor
Todd Kitten
Fifth Advisor
Tomasz Kordula
Abstract
Anaplasma phagocytophilum is an obligate intracellular bacterium that invades neutrophils to cause granulocytic anaplasmosis. The invasin-receptor pairs that facilitate uptake and hence disease are incompletely defined. Here we show that the invasin A. phagocytophilum invasion protein B (AipB), mediates bacterial entry and is important for infection in vivo. The AipB host cell interacting domain was narrowed down to amino acids 109 to 129 and CD18 was identified as its binding partner. A. phagocytophilum invasion protein A (AipA) orchestrates entry by engaging an unknown receptor. Yeast two-hybrid screening suggested that AipA binds CD13. The AipA-CD13 interaction induces Src phosphorylation, which is key for infection. While Src is established as critical for invasion, the mechanistic underpinnings of Src-dependent entry and the kinase’s roles in A. phagocytophilum infection cycle progression are unknown. Host cell caveolin-1 and the A. phagocytophilum type IV secretion system effector AnkA are Src substrates that have been implicated as important for host cell invasion. Antibody blocking of CD13 inhibits caveolin-1 phosphorylation and pharmacological inhibition modestly reduces infection. Antibody blocking of CD13 and CD18 reduces AnkA phosphorylation. Protein disulfide isomerase, another A. phagocytophilum interacting partner, is necessary for AnkA delivery. A. phagocytophilum development is dependent on parasitism of trans-Golgi vesicles. Src is known to promote trans-Golgi vesicular trafficking via dynamin 2 (Dyn2). Pharmacological inhibition of Dyn2 prevents trafficking to the Anaplasma vacuole. These findings illustrate the importance of Src to A. phagocytophilum invasion and development, which could have translational benefits that may be applied to protect against multiple infectious diseases.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-5-2026