10 March 2023

Identifying Genetic Markers to Detect Bacterial Infection Using the Collaborative Cross Mouse Model

Researcher to Watch: Elke Bergmann-Leitner, MSC, PhD

 

Tickborne diseases are gaining worldwide attention due to an increase in global temperatures and changes in tick populations with faster reproduction rates. Pathogens transmitted by ticks include bacteria such as the unusual type of Rickettsia bacteria that can live only inside the cells of another organism. Rickettsia bacteria mostly spread through ticks, mites, fleas, or lice, can cause diseases such as Rocky Mountain spotted fever, epidemic typhus, ehrlichiosis, and Mediterranean spotted fever.

Rickettsial diseases are difficult to diagnose, even by health care providers experienced with these pathogens. Most symptomatic rickettsial diseases cause moderate illness, but some like Rocky Mountain and Brazilian spotted fevers, Mediterranean spotted fever, scrub typhus, and epidemic typhus may be fatal in 20%–60% of untreated cases.

Elke Bergmann-Leitner, MSC, PhD has dedicated her career to identifying immune correlates of protection against infectious diseases and understanding the interplay between pathogens and the host immune system. Dr. Bergmann-Leitner is the Chief of the Immunology Core at the Center for Infectious Disease Research at Walter Reed Army Institute of Research (WRAIR). The mission of the Immunology Core at WRAIR is to evaluate immune responses either induced by vaccines to identify immune correlates of protection against infectious diseases or induced by pathogens identify biomarkers of infection.

In a Geneva-managed study titled “Identification of Genetic Markers of Susceptibility to Intracellular Bacterial Infection Using the Collaborative Cross Mouse Model,” in collaboration with Dr. Sean Riley at the University of Maryland, Dr. Bergmann-Leitner is conducting foundational studies which have identified mouse strains that are both susceptible and resistant to Rickettsia. Through an award funded by the National Institutes of Health (NIH) under award number 1R21AI171817-01, Geneva provides project management, regulatory oversight, and managing procurement needs.

Dr. Bergmann-Leitner said collaborative cross mice have proven to be an invaluable tool for studying the role of host genetics in a variety of infectious diseases. “This seminal work has established clear phenotypic variation in mouse susceptibility to infection and forms a strong foundation for employing forward genetic analyses of mouse susceptibility to identify aspects of the mammalian immune system that contribute to the effective immune response to infection,” she added.

Currently, the collaborative cross consortium reports more than 75 distinct collaborative cross mouse lines have been generated, capturing about 90% of variations in the mouse genome with equitable diversity distributed across the genome.

In the study abstract, Dr. Bergman-Leitner writes that “Assessing susceptibility to Rickettsia infection and immune response in these mice will: (1) identify collaborative cross mice that reproduce variability in both human disease and immune responses that will provide reliable mouse models to study variable host responses to prophylactic and therapeutic interventions, and (2) identify highly resistant vs. highly susceptible mice, which is the prerequisite for the identification of host genetic factors governing susceptibility to infection.”

Throughout her career, Dr. Bergmann-Leitner has unveiled several immune escape mechanisms which interfere with the induction or persistence of protective immunity. She has authored or co-authored publications and book chapters over 150 publications that have been cited more than 5,000 times and serves as editorial board member for several high-impact journals.

In another Geneva-managed study and subaward with Thomas Jefferson University, she is looking at establishing the serological landscape and their functional activity induced by SARS-CoV2 infections or vaccination, which is critical for our understanding and efforts in developing COVID-19 diagnostics, treatments, and vaccines. This NIH award 1R21HD107761-01A1 presents a unique opportunity to leverage advanced immuno-profiling methods developed at WRAIR to study the full spectrum of COVID-19 cases for an at-risk population (i.e., pregnant and breastfeeding women) at a major urban hospital center.

 

Disclaimer: The views expressed do not reflect the official policy of the Department of Defense or the U.S. Government.