Project Grant F32AI202963

TOWARDS OPTIMIZED MEDICAL DEVICE SURFACES: A STUDY ON THE IMPACTS OF SURFACE MICROTEXTURE ON BACTERIAL EXPLORATION, ATTACHMENT, AND COLONIZATION BIOLOGY - PROJECT SUMMARY / ABSTRACT NEW TOOLS ARE NEEDED TO PREVENT MEDICAL DEVICE-ASSOCIATED INFECTIONS SUCH AS CATHETER-ASSOCIATED URINARY TRACT INFECTIONS, CENTRAL LINE-ASSOCIATED BLOOD STREAM INFECTIONS, AND VENTILATOR ASSOCIATED PNEUMONIA, AMONG OTHER INFECTIONS ASSOCIATED WITH THE TREATMENT OF UROLOGICAL AND CARDIAC CONDITIONS. THESE INFECTIONS EVOLVE FROM THE COLONIZATION OF DEVICE SURFACES BY MICROBES, WHICH FORM TREATMENT- RECALCITRANT BIOFILMS THAT CAN SEED ACUTE CARE EMERGENCIES, INCLUDING SEPSIS. A PROPOSED SOLUTION FOR THIS PROBLEM IS TO OPTIMIZE THE DESIGN OF DEVICE SURFACES USING COLONIZATION-LIMITING MICROTEXTURES OR MICROPATTERNS, 3-D MICRON-SCALE FEATURES THAT DECREASE MICROBIAL BURDEN ON A SURFACE. THIS PROJECT AIMS TO UNDERSTAND HOW THE SPECIFIC TRAITS OF MICROTEXTURES INFLUENCE SURFACE COLONIZATION AND BIOFILM-FORMATION BIOLOGY OF MICROBES TO INFORM THE RATIONAL DESIGN AND ACCELERATE THE GENERATION OF OPTIMIZED MEDICAL DEVICE SURFACES. MY PRELIMINARY EVIDENCE AND PUBLISHED LITERATURE SUPPORT THAT MICROBES RESPOND TO THEIR PHYSICAL ENVIRONMENTS, INCLUDING SURFACE TEXTURE. IN MY PRELIMINARY WORK, I HAVE DEVELOPED A MICROTEXTURE FLOW CELL LIBRARY, USED TO TEST THE BIOLOGICAL IMPACTS OF MICROTEXTURE, SPECIFICALLY THE HYPOTHESIS THAT MICROTEXTURES MODIFY BIOFILM FORMATION BY INTERRUPTING SURFACE-SENSING SIGNAL TRANSDUCTION, AND THE PHENOTYPIC DYNAMICS THAT EVOLVE FROM THESE SIGNALING PROCESSES. THE PROPOSED RESEARCH PLANS TEST THE FOLLOWING HYPOTHESES IN 2 SPECIFIC AIMS: 1) TEST THE HYPOTHESIS THAT COLONIZATION-MODIFYING MICROTEXTURES ALTER INTRACELLULAR CONCENTRATIONS OF SURFACE SENSING SIGNALS, AND 2) INVESTIGATE SURFACE ASSOCIATED MOTILITY MODIFICATION BY MICROTEXTURES. ALL AIMS ARE TESTED BY COMPARISON TO SMOOTH CONTROLS OR WILD TYPE STRAINS IF UTILIZING MUTANTS. A KEY LONG-TERM OBJECTIVE OF THIS PROJECT IS TO USE THE INFORMATION DEVELOPED HERE TO DESIGN SURFACES THAT CAN MODIFY MICROBIAL COLONIZATION DYNAMICS OF MEDICAL DEVICES, INDUSTRIAL EQUIPMENT, AND THE ENVIRONMENT. THIS PROJECT AND MY TIME IN THE O'TOOLE LAB PROVIDE OUTSTANDING TRAINING OPPORTUNITIES IN MICROBIOLOGY, IMAGE ANALYSIS, PROJECT AND COLLABORATOR DEVELOPMENT, TOOL ESTABLISHMENT, AND MENTORSHIP, FACILITATING MY TRANSITION FROM POSTDOC TO INDEPENDENT PI.