Cellular differentiation in biofilms
Biofilms are multicellular microbial communities that represent the most common lifestyle of many microorganisms. Biofilms can persist in a wide range of environments in part because they contain differentiated subpopulations of cells that serve defined roles in the microbial community to promote the overall health of the biofilm.
Through collaborations with mass spectrometry experts at Vanderbilt University, we have identified a number of previously uncharacterized P. aeruginosa biofilm subpopulations via the application of a newly emerging technology known as MALDI imaging mass spectrometry. We hypothesize that these subpopulations exist in order to withstand environmental insults that P. aeruginosa encounters in one or more of the many niches known to be occupied by this opportunistic pathogen. We seek to determine the role of these subpopulations in biofilm architecture and survival/persistence in the presence of various environmental stressors.
Microbial interactions during infection
During infection, invading pathogens experience various environmental stresses and are often found in polymicrobial communities. Within the various microenvironments of the human host, pathogens and commensals both compete and cooperate in order to combat the stresses experienced during infection.
Our studies focus on Pseudomonas aeruginosa and Staphylococcus aureus interactions because these pathogens often co-infect sites ranging from diabetic foot ulcers to the cystic fibrosis lung and therefore represent a substantial medical problem. We hypothesize that cooperation between these organisms is occurring within select microenvironments sampled during infection. We seek to understand the specific mechanism underlying co-infection (for example, the repression of P. aeruginosa production of anti-microbial compounds), and to determine whether or not P. aeruginosa and S. aureus can act cooperatively within certain host microenvironments in order to exacerbate the disease.
Metalloregulation of bacterial physiology
Environmental metal fluctuation is one of the primary signals sensed by bacteria to assess entry into a new and challenging environment. This is especially true for pathogens entering the host environment as host-induced metal starvation is an innate immune response designed to limit the growth of invading microorganisms.
We have previously shown that metal-limitation induced by the immune protein calprotectin promotes P. aeruginosa and S. aureus co-culture and that metal fluctuations within P. aeruginosa biofilms are responsible for much of the observed cellular differentiation within biofilm communities. We seek to determine the mechanisms by which metal levels are sensed in order to elicit these physiological responses.