Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

BACKGROUND: Spirochetes are invasive, fast-moving gram-negative-like bacteria with a helical or planar wave-form shape, internal periplasmic flagella that wrap around the cell body and drive movement by undulating wave- or corkscrew-like rotation of the cell body, and a fluid outer membrane containing few transmembrane proteins. Most spirochete adhesion proteins (adhesins) are anchored to the outer membrane by lipid anchors and are likely highly mobile. Spirochetes move faster in dense biological materials than in pure liquid, possible due to traction-conferring adhesive interactions between cells and their extracellular environment, a property that may be crucial for colonization of environments inaccessible to other bacteria. If motility depends on adhesion, then adhesins may also be mobile, especially under conditions such as adhesion to surfaces under flow in which bacterial motility and flow propel the cell body forward as the adhesion complex anchoring bacteria to surfaces remains in a fixed position. The properties and mechanisms underlying dynamic coordination of spirochete adhesion and motility in the presence and absence of flow are not yet defined, and have not been defined for most bacteria. This is largely due to the need to develop rapid, high resolution live cell imaging tools to study coordination of adhesion and motility. My laboratory is expert in developing imaging-based approaches for studying bacterial adhesion, motility and movement in flow and non-flow environments, and recently established the first imaging-based particle-tracking and biophysical analysis tools to studying bacterial adhesion and movement to surfaces under flow. We work primarily with the Lyme disease spirochete Borrelia burgdorferi ( Bb ), have identified multiple adhesins and extracellular matrix components targeted by these bacteria during movement, and found, unexpectedly, that Bb motility stimulates and stabilizes Bb interactions with endothelial cells under flow.

OVERALL OBJECTIVE OF RESEARCH PROGRAM: To investigate the fundamental properties and mechanisms underlying coordination of adhesion and motility in Bb . Short-term objective: Develop rapid, high speed live cell imaging-based methods to study bacterial coordination of adhesion and motility. Long-term objective: Apply these methods to investigate how bacterial motility promotes adhesion to surfaces under flow, and how adhesion and motility are coordinated.

SIGNIFICANCE: These studies will provide the first dynamic insight into mechanisms coordinating motility and adhesion in spirochetes. This research will be of fundamental, non-health-related interest for Canadian microbiologists, especially because it will establish methods useful for studying coordination of adhesion and motility in other bacteria, including those that form industrially- and medically-important flow-resistant biofilms.