Walker Lab

The Walker lab is focused on understanding the host-pathogen interactions that dictate the onset, course, and outcome of chronic infections. Our work uses infections of medical devices as a model for chronic disease. By defining the bacterial and host mechanisms that facilitate these recalcitrant infections, we seek to develop novel antibiotic sparing therapies that can effectively treat common and costly diseases. We use a multidisciplinary approach to blend the use of basic science, model systems, and patient samples to pursue the following questions:

1. How do medical devices render people susceptible to infection?

Millions of medical devices are placed every year and their use is expected to increase due to their efficacy at improving the length and quality of life. However, infection of medical devices is a common, dreaded complication. Furthermore, it is a well-known phenomenon that medical devices render people susceptible to atypical or “less pathogenic” bacteria, yet the mechanisms responsible remain largely unknown. Our recent studies indicate the device itself induces inflammation, which may prevent the host from mounting an effective response against these “less pathogenic” bacteria, allowing them to cause disease. To define these interactions, we are combining the use of model systems and patient samples to understand the inflammatory response to devices with and without infection. This work involves immunology, microbiology, and biochemistry for the identification of biomarkers that predict infection risk and the development of better device materials that reduce infections.

2. What are the bacterial mechanisms that promote medical device infections?

Staphylococci are the primary cause of device infections and form recalcitrant biofilms on the device surface. Our group recently discovered that staphylococci use different virulence mechanisms to initiate biofilm formation, including adhesins to attach to various host proteins coating device surfaces as well as enzymes like urease, which provide additional substrates for attachment. This work uses bacterial genetics and molecular microbiology to understand the host-pathogen-device interactions that facilitate infection to develop novel antibiotic-sparing treatment strategies.

3. What therapeutic strategies are effective against medical device infections?

Medical device infections are recalcitrant to antibiotic therapy, with the current gold standard of treatment relying on device removal. Thus, prevention strategies using antibiotic coatings or washes have become popular among surgeons. Our group recently discovered that antibiotic pocket irrigants used during breast reconstruction post-mastectomy can enhance biofilm formation among clinically derived infection isolates and do not prevent infection in an animal model. We collaborate closely with physicians and use a combination of model systems, patient samples, and genomics to understand how bacteria establish infections that are recalcitrant to antibiotic therapy and translate these discoveries into better prevention and/or treatment strategies.