Research

Polymicrobial Interactions Affecting Bacterial Behaviors

Interspecies interactions can affect bacterial behaviors.

Interactions between co-infecting bacterial pathogens
Bacteria often exist in multispecies communities, where polymicrobial interactions influence antibiotic resistance, motility, lifestyle, and other bacterial behaviors. Despite this, many species are studied in isolation and therefore many of the molecules underlying interspecies interactions as well as the unique behaviors that emerge in native environments have not been deciphered. Pseudomonas aeruginosa and Staphylococcus aureus are co-infecting pathogens that frequently cause chronic, antibiotic resistant infections in the respiratory tracts of people with cystic fibrosis. We are interested in defining novel molecules that play important roles in modifying bacterial behaviors in this two-species system and others, and determining how bacteria respond to interactions within these communities. This research will ultimately enhance our understanding of bacterial communication and reveal new targets to disrupt persistent bacterial infections.

Mechanisms of Bacterial Competition Strategies

Mechanisms of bacterial antagonism.

Arsenal of bacterial weapons as potential antimicrobials
Antibiotic resistance is a global health problem that makes it harder to treat infections, so there is an urgent need for new therapeutics. To compete for nutrients and space in communities, bacteria have evolved diverse strategies to kill one another. By studying the weapons made by bacteria, we aim to discover and design new drugs that can be used to treat infections. With the rise in antibiotic resistance, there is increased enthusiasm in phage and phage-like therapy research. We are interested in determining how bacteria regulate the production of a phage-like bacterial weapon that is used to kill neighboring cells, called a 'tailocin'. We are also defining the molecular mechanisms underlying susceptibility to tailocins in order to potentially engineer these microbial weapons as innovative technologies to combat bacterial infections.

Regulation of Phenotypic Heterogeneity

Genetically identical bacterial populations exhibit phenotypic heterogeneity.

Additional levels of regulation governing heterogeneity in bacterial communities
Within bacterial communities, different cells can specialize to perform unique jobs such as producing matrix or metabolites, exhibiting motility, or retaining a dormant state and antibiotic tolerance. This helps bacteria provide a division of labor and survive environmental stressors. However, how bacteria control distinct subpopulation phenotypes are not fully realized. We hypothesize that along with inherent stochasticity, there are checkpoints of regulation that maintain heterogeneity. We are using single-cell and population-based approaches to identify the molecular mechanisms underlying phenotypic heterogeneity. This work will illuminate novel pathways as therapeutic targets.