Bridging Pathogens and Progress in Lyme Disease Research

By Mase Peterson

Since establishing her lab at Tufts University School of Medicine in 2012, Bree Aldridge, professor of molecular biology and microbiology at TUSM and professor of biomedical engineering at the School of Engineering, has tackled the complexities of bacterial pathogens, developing innovative therapies for tuberculosis. Now, through the Tufts Lyme Disease Initiative, Aldridge brings her unique perspective and multidisciplinary background to explore the survival strategies of Lyme disease-causing bacteria. Her aim is to revolutionize treatment strategies and deepen our understanding of bacterial pathogenesis. This collaborative group of faculty, staff, and students is dedicated to eliminating the public health threat of Lyme disease by 2030.

Tufts is home to one of the world’s most comprehensive groups of tick-borne disease researchers. Led by co-directors Linden Hu, Paul and Elaine Chervinsky Professor of Immunology, and Robert P. Smith, a physician at Maine Medical Center and professor of medicine, the team recently secured a $20.7 million federal grant, further solidifying Tufts’ position as a global leader in Lyme disease research.

In this Q&A, part of a feature series spotlighting members of the Initiative, Professor Aldridge discusses her groundbreaking research, the collaborative efforts driving the Initiative, and her aspirations for the future of Lyme disease treatment and prevention.

Tell us about your background and what brought you to TUSM.

“I grew up in Arizona and love to find patterns in data – this is why I enjoy looking at systems-level data in cell biology so much. I am trained as an engineer and a biologist, and I started my lab at TUSM with a joint appointment in Tufts University School of Engineering. My lab has focused on using computational and quantitative cell biological approaches to develop improved therapies for tuberculosis. To achieve this, we need to understand how the bacteria that cause tuberculosis tolerate the stress imposed by antibiotics and the host environment. We study how these bacteria grow and divide in different environments and how growth behaviors determine drug susceptibilities. We also develop and apply tools for early-stage drug development that enable us to learn how antibiotics kill bacteria and to design more effective drug combinations.

Though the bacteria that cause Lyme disease is different from the bacteria that cause tuberculosis, there are several aspects of how they strategize to survive in the host that are similar. I joined the Tufts Lyme Disease Initiative because I want to explore how studying a cross-section of pathogens can enhance our understanding of bacterial pathogenesis and improve treatment strategies.”

What is your role in the initiative and is your team focusing on any specific aspects of Lyme disease research?

“As part of the Tufts Lyme Disease Initiative, my lab and I are adapting early drug development tools (originally designed for application in tuberculosis) to understand drug action mechanisms and design combination therapies, applying our knowledge from tuberculosis to Lyme disease. These connections have really been solidified by Trever Smith, who did his postdoc work with my lab on tuberculosis after studying Lyme disease in his graduate studies. I have really enjoyed learning about the intricacies of Lyme disease from him!

Imaging has been an essential tool for studying bacterial growth behaviors and response to drug treatment in our work on tuberculosis. But whereas the bacteria that cause tuberculosis are rod shaped, the bacteria that cause Lyme disease are spirochetes, giving my lab a new cell shape to study and to design early drug development tools around.”

What do you hope this research will achieve for patients with chronic Lyme disease and the medical community?

“I hope we will form a better understanding of how variation is created in the bacteria that cause Lyme disease and then use that information to develop improved, targeted therapies. Tuberculosis is a chronic infection, so I believe that we can translate knowledge about how the tuberculosis bacteria survive in different host environments to the Lyme disease-causing bacteria (and vice versa).”

What challenges do you foresee and how are you addressing them?

“The Lyme disease spirochetes (bacterial cells) are difficult to work with due to their unique characteristics, requiring innovative growth and measurement protocols. I think we will need to be creative in designing new, scalable and efficient techniques for growing and studying Lyme disease bacteria in the lab, similar to those used for model organisms.

Fortunately, the team at the Tufts Lyme Disease Initiative is a dynamic and multidisciplinary group of researchers and clinicians. Their diverse expertise and enthusiasm bring a lot of energy to tackling these challenges. Brainstorming with them is incredibly rewarding and fun, as we collectively devise new strategies to overcome these obstacles.”