Event
PhD Dissertation Defense: Talia Solomon
Tuesday, May 12, 2026
1:00 p.m.
AJC 5104 (5th floor conference room)
Title: Investigating the therapeutic potential of extracellular vesicle - microbe interactions
Committee members:
Associate Professor Dr. Steven M. Jay, Chair
Associate Professor Dr. Gregg Duncan
Assistant Professor Dr. Hannah Zierden
Professor Mary-Claire Roghmann, MD, MS
Associate Professor Dr. Amy Karlsson, Dean’s Representative
Abstract:
Within the landscape of infectious disease, extracellular vesicles (EVs) from pathogenic sources can cause damage to the host and modulate the immune response to infection. Additionally, EVs from pathogens have been studied as potential vaccine candidates. While the understanding of the role of EVs within infection has been explored in the context of pathogen effects on the host, there is little known about the opposite direction of transport, host EV effects on pathogens, as well as the role of commensal derived EVs on pathogens. With that in mind, we have aimed to provide foundational information about the potential of EVs from both host and commensal sources on microbial pathogens. The larger contextual question we have aimed to answer is whether these EVs have potential as antimicrobial therapeutics. This research was motivated by the limitations of current antimicrobial treatments, due to rapidly rising resistance, the risk of emerging pathogens, as well as the significant side effect burden of existing second line therapeutics. Additionally, we believe EVs possess beneficial qualities allowing them to hopefully overcome some of the current limitations of antimicrobial therapeutics. EVs are inherently multimodal in effect due to their varied cargo representative of their cell source of origin. Furthermore, the current literature demonstrates inherent antimicrobial effects of EVs to be narrow in spectrum activity. Additionally, EV engineering technology can be leveraged to produce specific antimicrobial cargo in EVs enhancing potency and increasing the number mechanisms of action from the baseline activity of EVs, limiting risk of resistance development. With this perspective in mind, we aimed to address the limited knowledge in the field through a combination of foundational experimental aims along with engineering proof of concepts. In the first arm of this project, the potential of host derived THP-1 monocyte derived EVs was shown to partially prevent biofilm formation by Pseudomonas aeruginosa (P. aeruginosa), a common nosocomial, multidrug resistant pathogen whose infections are significantly harder to treat due to recalcitrant biofilm formation. We demonstrated that THP-1 EVs and induced pluripotent stem cell-derived mesenchymal stromal/stem cell (iMSC) EVs shared an ability to prevent biofilm formation that was not present in HEK293T EVs. Secondly, we explored the antagonistic effects of Lactobacillus subspecies (spp.) Limosilactobacillus reuteri (L. reuteri) and Lactiplantibacillus plantarum (L. plantarum) derived EVs against the opportunistic pathogens Candida albicans (C. albicans) and Candida glabrata (C. glabrata). We demonstrated an anti-adhesion effect of the EVs endogenously against C. albicans biofilm adherence. We also explored EV uptake which occurred for all EVs tested and was limited by decreased temperature and energy restriction. Finally, we demonstrated that EVs from L. plantarum could be engineered to produce antifungal proteins leading to decreased metabolic activity and hyphal formation. Overall, this work addresses the endogenous potential of both host and commensal derived EVs against bacterial and fungal pathogens respectively. Additionally, we demonstrated a comprehensive exploration of the interactions between Lactobacillus EVs and Candida spp. Finally, we provided a proof of concept for EV engineering for delivery of antifungal cargo. These findings advance our understanding of how EVs directly impact microbial pathogens and can be leveraged as novel antimicrobial agents.
Committee members:
Associate Professor Dr. Steven M. Jay, Chair
Associate Professor Dr. Gregg Duncan
Assistant Professor Dr. Hannah Zierden
Professor Mary-Claire Roghmann, MD, MS
Associate Professor Dr. Amy Karlsson, Dean’s Representative
Abstract:
Within the landscape of infectious disease, extracellular vesicles (EVs) from pathogenic sources can cause damage to the host and modulate the immune response to infection. Additionally, EVs from pathogens have been studied as potential vaccine candidates. While the understanding of the role of EVs within infection has been explored in the context of pathogen effects on the host, there is little known about the opposite direction of transport, host EV effects on pathogens, as well as the role of commensal derived EVs on pathogens. With that in mind, we have aimed to provide foundational information about the potential of EVs from both host and commensal sources on microbial pathogens. The larger contextual question we have aimed to answer is whether these EVs have potential as antimicrobial therapeutics. This research was motivated by the limitations of current antimicrobial treatments, due to rapidly rising resistance, the risk of emerging pathogens, as well as the significant side effect burden of existing second line therapeutics. Additionally, we believe EVs possess beneficial qualities allowing them to hopefully overcome some of the current limitations of antimicrobial therapeutics. EVs are inherently multimodal in effect due to their varied cargo representative of their cell source of origin. Furthermore, the current literature demonstrates inherent antimicrobial effects of EVs to be narrow in spectrum activity. Additionally, EV engineering technology can be leveraged to produce specific antimicrobial cargo in EVs enhancing potency and increasing the number mechanisms of action from the baseline activity of EVs, limiting risk of resistance development. With this perspective in mind, we aimed to address the limited knowledge in the field through a combination of foundational experimental aims along with engineering proof of concepts. In the first arm of this project, the potential of host derived THP-1 monocyte derived EVs was shown to partially prevent biofilm formation by Pseudomonas aeruginosa (P. aeruginosa), a common nosocomial, multidrug resistant pathogen whose infections are significantly harder to treat due to recalcitrant biofilm formation. We demonstrated that THP-1 EVs and induced pluripotent stem cell-derived mesenchymal stromal/stem cell (iMSC) EVs shared an ability to prevent biofilm formation that was not present in HEK293T EVs. Secondly, we explored the antagonistic effects of Lactobacillus subspecies (spp.) Limosilactobacillus reuteri (L. reuteri) and Lactiplantibacillus plantarum (L. plantarum) derived EVs against the opportunistic pathogens Candida albicans (C. albicans) and Candida glabrata (C. glabrata). We demonstrated an anti-adhesion effect of the EVs endogenously against C. albicans biofilm adherence. We also explored EV uptake which occurred for all EVs tested and was limited by decreased temperature and energy restriction. Finally, we demonstrated that EVs from L. plantarum could be engineered to produce antifungal proteins leading to decreased metabolic activity and hyphal formation. Overall, this work addresses the endogenous potential of both host and commensal derived EVs against bacterial and fungal pathogens respectively. Additionally, we demonstrated a comprehensive exploration of the interactions between Lactobacillus EVs and Candida spp. Finally, we provided a proof of concept for EV engineering for delivery of antifungal cargo. These findings advance our understanding of how EVs directly impact microbial pathogens and can be leveraged as novel antimicrobial agents.
