Research

Our research program focuses on the cell biology of different bacterial species that are causes of infectious diseases in humans and other hosts. The foundations of our research program began by identifying and analyzing the colonization and virulence determinants of Campylobacter jejuni. These factors are known to be required for colonization of the avian host to lead to commensalism and/or infection of the human host to cause diarrheal disease. We also explore how transcription of many of these C. jejuni genes are accurately regulated.

While these projects in C. jejuni remain major emphases of our research program, we have expanded our focus over time into other bacterial pathogens such as Vibrio cholerae and Pseudomonas aeruginosa. Currently, we have many active research projects that delve into a wide range of interesting aspects of microbial cell biology of bacterial pathogens. These areas include:

  • Understanding signal transduction pathways common to bacterial pathogens
  • Determining in vivo stimuli such as microbiota-generated metabolites sensed by bacterial pathogens
  • Identifying and unraveling unique sensory mechanisms of bacterial pathogens required for infection
  • Analyzing how polar flagellar motors are constructed in many pathogens
  • Understanding the form and function of high-torque flagellar motors
  • Monitoring communication between macromolecular complexes in the bacterial cell
  • Identifying new virulence determinants of bacterial pathogens
  • Determining molecular mechanisms of spatial and numerical regulation of flagellar biogenesis in bacteria

    The bacterial flagellum is one of only three known reversible rotary motors produced in nature. Many bacterial species produce a flagellar motor with a commonly conserved core structure that includes the inner membrane-bound secretion system, the flagellar rod and hook, and the extracellular filament. Even though these core flagellar structures are conserved in different bacteria, the functional outputs of these motors can vary across species. For instance, flagellar motors produced by E. coli and Salmonella promote efficient swimming motility in low viscosity environments. However, other bacteria such as Campylobacter jejuni produce flagellar motors that promote swimming motility as efficiently as E. coli in the low-viscosity milieu and also enable augmented motility velocities in higher viscosities that normally paralyze other flagellated bacteria.

    Formation and Function of High-Torque Flagellar Rotary Motors

    Campylobacter jejuni is a leading cause of bacterial diarrheal disease in humans in the United States and other developed countries throughout the world. Upon infection of humans, C. jejuni adheres to and invades colonic epithelial cells resulting in inflammation and diarrhea.

    Interactions Between Campylobacter jejuni and Hosts

    The host and the intestinal microbiota form a complex, interacting ecosystem so that nutrients are exchanged and protection is provided for each to maintain health and homeostasis. New bacteria introduced into the ecosystem must overcome both physical and metabolic hurdles to establish a niche in this ecosystem.

    Campylobacter jejuni is a commensal organism in the intestinal tracts of many animals in the wild and agriculture, including avian, bovine, and porcine species. However, infection of the human intestinal tract often progresses to diarrheal disease. Although the outcomes of infection are different, C. jejuni colonizes the lower intestinal tract of both the human and avian intestinal tracts. To colonize these areas, C. jejuni must identify favorable niches that support growth by recognizing specific nutrients and other components. Proper signaling networks in the bacterium must be able to sense specific cues and then alter gene transcription accordingly to promote colonization.

    Metabolite Sensing

    Peritrichous bacteria such as E. coli and Salmonella species historically have served as models for understanding many aspects of flagellar gene transcription and biosynthesis. Alternatively, some important bacterial pathogens such as Campylobacter jejuniHelicobacter pyloriVibrio cholerae, and Pseudomonas aeruginosa are polar flagellates. These bacteria are genetically programmed to produce only a limited number of flagella at polar regions to create specific flagellation patterns. V. cholerae and P. aeruginosa synthesize a single flagellum only at one pole (monoflagellation),  C. jejuni produces a single flagellum at both poles (amphitrichous flagellation), and H. pylori produces a tuft of flagella at a single pole (lophotrichous flagellation).

    Programming Polar Flagellar Biogenesis