Beyond Genetics: Lyme Disease's Unexpected Role in Connective Tissue Health - Findings from a Murine Model for Borrelia Burgdorferi Infection and the Human Clinical Study MAESTRO

Qingying Feng – Icahn School of Medicine at Mount Sinai; Kunzan Liu – Massachusetts Institute of Technology; Guido Pisani – Massachusetts Institute of Technology; Beth Pollack – Massachusetts Institute of Technology; Sixian You – Massachusetts Institute of Technology; Michal Caspi Tal – Massachusetts Institute of Technology

Abstract Text: Borrelia burgforferi (Bb) infection-associated chronic illness affects an estimated 2 million people in the US, and it is challenging to distinguish between immune vs pathogen mediated pathomechanisms. Label-free imaging of tissues from older (reproductively senescent) female C3H/HeJ mice infected long-term with Bb, revealed the presence of the bacteria in the connective tissues and indicators of pathology via gross anatomy and microscopic analysis. The use of a bioluminescent strain of Bb allowed for the identification of infected tissues in vivo, and these tissues were then imaged ex vivo via Label-free microscopy and orthogonally validated with histology. A hypermobile tail phenotype was observed to be infection status, age, strain, and sex specific, with distinct immune cell populations and features. Tensile testing revealed a strong inverse correlation between bacterial load and necessary force required to stretch the tissue. In our clinical study, MAESTRO, analysis of participants' previous medical history survey results identified a correlation between Bb infection-associated chronic illness and sequelae of hypermobility disorders in individuals who had Lyme disease, received antibiotics and never recovered. These data call into question a longstanding assumption that hypermobility disorders are in large-part benign and genetic, and suggest that previous Bb infection may play a role in the development of these diseases.