The Questions We Are Currently Exploring

Recently the idea of studying microbial competition, both in vivo and ex vivo, has gained traction to devise new narrow-spectrum therapeutics that selectively target the pathogen of interest in a practice termed Microbial Ecology Medicine. Our focus is in dissecting microbial interactions using both genetic and biochemical techniques. We use the microbes that inhabit the human oral cavity as a model system that has several clear advantages: (i) most members of the early dental biofilm can be easily manipulated genetically, (ii) these microbes require a low biosafety level to study in a wet-lab setting, making them fantastic projects for early trainees (iii) they have fast growth rates so data and replications of the resulting data can be generated quickly, and (iv) can be studied in simple in vitro or ex vivo systems that mimic their growth in either saliva alone or on hard surfaces such as hydroxyapatite disks that is the main inorganic constituent of tooth enamel.  

Despite great advancements, significant oral health and wellness issues remain in communities all over the world, particularly among under-privileged groups. Dental caries, along with periodontal diseases, have historically been considered one of the most important global oral health burdens. Dental caries remains the most common infectious disease of children and adults within the United States. It is well established with recent research achievements that dental caries is associated with compositional changes in the microbiota colonizing the oral cavity, with certain types of microbial communities being present in health and others in disease. Among these changes is an increase in the proportion of Streptococcus mutans, which possesses the ability to tolerate and persist during production of organic acid end products as a result of fermentation that will demineralize the tooth enamel with prolonged exposure. Perturbations brought by the lowering of plaque pH drives dysbiosis in the microbial community, decreasing the amounts of health-associated Streptococcus species that confer protection from caries through arginine metabolism via the arginine deiminase (ADS) pathway as well as antagonism against S. mutans through multiple strategies including hydrogen peroxide production. Concurrently an increase of taxa, such as S. mutans, Veillonella spp., and Lactobacillus spp. that retain aciduric and acid tolerant traits, propagate shifts in microbial composition. Emergence of these species within the dental plaque accelerates the rate of net acid demineralization that outpaces remineralization, leading to clinical disease. Thwarting the appearance of these disease-related organisms while keeping the normal flora intact remains a chief strategy towards caries prevention.

Here are some of our current projects surrounding these topics: 

Oral Commensals Altering Streptococcus mutans Gene Expression

We have recently detailed a conserved transcriptomic response by S. mutans when grown in coculture with other oral streptococci. Current investigations revolve around understanding how a pathogen in S. mutans senses competitors. 

Spatial Organization within Oral Biofilms

Streptococcus mutans forms microcolonies during biofilm formation. However, coculturing S. mutans with different commensal streptococci can influence microcolony shape and size. We are currently exploring what factors influence this spatial organization. 

Cell-Cell Signaling in Oral Biofilms

Gram-positive bacteria use short, hydrophobic peptides (sometimes termed pheromones) to synchronize behaviors among the population. This cell-cell signaling controls critical behaviors such as genetic competence, sporulation and toxin production. We are defining the processes and mechanisms by which oral bacteria utilize this form of communication.

 

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