Characterization and intervention strategies of Campylobacter jejuni biofilm in a microfluidic "lab-on-a-chip" system

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Campylobacter jejuni is the leading cause of foodborne bacterial gastroenteritis in the developed world, with diarrhea often associated with consumption of undercooked poultry products, drinking water and unpasteurized milk. It is estimated that 1% of Canadian population is affected with campylobacteriosis each year, resulting in significant burden on economy because of lost productivity and the potential for serious medical complications. Residing in a biofilm microenvironment is a critical way for this microaerophilic pathogen to survive and transmit into the food chain in stressful conditions, such as the natural aerobic environment, leading to food poisoning. Biofilm formation allows bacteria to grow and survive, as the surface-attached and matrix-encased bacteria are protected. My overall research program is to understand the behavior of C. jejuni in the environment, food systems and animals, and to develop mitigation strategies to reduce campylobacteriosis. The aim of this research proposal is to use novel approach and advanced technology to characterize C. jejuni biofilms and develop intervention strategies. Our central hypothesis is that natural compounds and synthetic polymers can inhibit C. jejuni biofilm formation driven by environmental and genetic factors. Our specific objectives in the first five-year period are to investigate oxygen condition that promotes C. jejuni biofilm formation, to identify and characterize C. jejuni colonization associated proteins involved in biofilm formation, to identify compounds as either antimicrobials or quorum sensing (QS) signal inhibitors, resulting in less C. jejuni biofilms, and to develop molecularly imprinted polymers (MIPs) as QS capturer to inhibit C. jejuni biofilms. We have established a microfluidic “lab-on-a-chip” platform coupled with biophysical instruments (i.e., confocal micro-Raman spectroscopy and atomic force microscopy) to cultivate and nondestructively characterize C. jejuni biofilms in a natural state. The work will allow us to better understand biofilm as an important vehicle for C. jejuni to survive during transit between hosts and on food products under unfavorable conditions and to further develop effective strategies to reduce biofilm formation. The studies address fundamental questions of bacterial stress, QS, and gene expression, and the knowledge to be generated is therefore of broad biological interest. The development of QS inhibitors and capturers will suggest new ways that food industry to reduce the prevalence of pathogens. For example, MIPs can be grafted onto food contact surfaces to reduce bacterial biofilms. Pharmaceutical company may also be able to design novel antimicrobials based on new target site (i.e., QS) while do not increase bacterial antibiotic resistance. This research has the potential for significant economic benefit to Canadian food producers and public health while increasing fundamental knowledge on bacterial biofilms that may translate to study other pathogens.