Abstract

Pathogenic bacterial extracellular vesicles (BEVs) are nanoscale particles derived from bacteria that contain pro-inflammatory cargo. During bacterial infections, BEVs provoke the host inflammatory response and may cause widespread damage. Furthermore, antibiotic treatment can boost BEV production and thereby increase the number of toxic signals traveling through the circulatory system. This is especially dangerous in brain blood vessels since evidence suggests that BEVs may destabilize the protective blood–brain barrier (BBB), resulting in neuroinflammation associated with cognitive decline and development of neurological disorders. Our understanding of BEV interactions with the host remains limited, necessitating the development of in vitro models to better understand their effects on human cells. Our work demonstrates that antibiotics modulate production of Escherichia coli–derived BEVs as well as packaging of pro-inflammatory cargo in a manner dependent on the bacterial strain and the class of antibiotics. These changes have pronounced effects on activation of human endothelial cells, causing increased expression of surface adhesion molecules that can attract immune cells and promote their transit from blood into surrounding tissues. Our identification of specific toxins incorporated in the BEVs may prove useful for future attempts to block their stimulatory effects. We model BBB interactions with BEVs using a microphysiological system featuring an ultrathin porous silicon nitride membrane. Human stem cell–derived brain microvascular endothelial cells demonstrate sensitivity to BEVs but still maintain a functional barrier after exposure. However, BEVs can indirectly disrupt the BBB by increasing the production of pro-inflammatory signals from immune cells. In other words, microphysiological models require an immune component for accurate assessments of BEV–initiated damage to the BBB. In the future, this work may serve as a basis for modeling therapeutic approaches to mitigate the effects of BEV–driven damage to blood vessels and brain tissues.

Publication Date

2-27-2026

Document Type

Dissertation

Student Type

Graduate

Degree Name

Biomedical and Chemical Engineering (Ph.D)

Department, Program, or Center

Biomedical Engineering

College

Kate Gleason College of Engineering

Advisor

Thomas R. Gaborski

Advisor/Committee Member

Vinay V. Abhyankar

Advisor/Committee Member

Kathleen A. Lamkin-Kennard

Campus

RIT – Main Campus

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