Josephine (Josie) Chandler

Research overview

Most bacteria are found in complex microbial communities, where they frequently interact with other members of the community. Bacterial interactions play a dramatic role in shaping microbial communities by changing population dynamics and influencing microbial community processes. Prior studies of microbial interactions have been primarily of single-clone populations, which provide a limited view of how interactions might influence more complex communities.

The development of laboratory models or ‘synthetic ecology’ approaches, in combination with genetics and genomics approaches, provide new opportunities to study bacterial interactions. The laboratory models offer a powerful but simplified approach to study multiple-strain and multiple-species communities in a controlled setting. These synthetic communities offer many advantages over direct studies of natural communities, which can present many challenges.

We use laboratory models to study interspecies competition and the evolution of cooperation in bacteria. We are also interested in understanding how bacteria communicate using chemical signals to coordinate competitive and cooperative behaviors. Our work focuses on several members of the Burkholderia genus, the soil bacterium Chromobacterium subtsugae and Pseudomonas aeruginosa, an opportunistic pathogen and the most common cause of fatality in patients with the genetic disease cystic fibrosis.

Cell-cell communication

Many bacteria communicate using small chemical molecules or ‘signals’ that transmit messages between cells. One of the mechanisms by which bacteria communicate is quorum sensing. Quorum sensing is a type of cell-cell signaling that regulates behaviors in a population density-dependent manner. Quorum sensing contributes to pathogenesis of many plant and animal pathogens and for this reason has been the target of efforts to develop novel antivirulence therapeutics. My work is broadly focused on how quorum sensing systems benefit bacteria in multispecies communities. We have shown that quorum sensing coordinates the production of toxins, which can be important for interspecies competition. We have also shown that quorum sensing controls antibiotic resistance, which can defend against competitors during competition. We are leveraging our laboratory models to understand how quorum sensing control of toxins and toxin resistance impacts the dynamics of competition. We are also interested in understanding how antibiotics contribute to the evolution of quorum sensing.

Antibiotic discovery

Many bacterial toxins are quorum sensing-controlled, such as the antibiotic bactobolin produced by B. thailandensis and hydrogen cyanide produced by P. aeruginosa. We are interested in understanding how bacteria use quorum sensing to coordinate production of these toxins and to compete with other strains and species. We are also interested in the chemistry and biology of these molecules, which are an important yet understudied facet of survival and pathogenesis of many soil microbes. Our work on antibiotics began with bactobolin, a potent, broad-spectrum antibiotic produced by B. thailandensis. We have since focused on other antibiotics – specifically, malleilactone, and more recently 4-hydroxy-3-methyl-2-alkylquinoline antibiotics, produced by B. thailandensis. We are also carrying out studies of hydrogen cyanide produced by P. aeruginosa and C. subtsugae.

Cooperation

Quorum sensing commonly regulates cooperative behaviors. Cooperative behaviors involve public goods that can be shared by all of the members of a population, including those that do not produce it. Public goods are available to everyone (an excellent example of a public good is National Public Radio). Those individuals that pay for the public goods are called cooperators. Those that utilize the public goods without paying are called cheaters. In the case of NPR and other true public goods, a certain number of cooperators are required to maintain production of the public good - if there are too many cheaters, the system will fail. In bacteria, common examples of public goods include extracellular factors such as proteases or antibiotics, or extracellular matrix material that holds a biofilm together. In bacteria these public goods are commonly regulated by quorum-sensing systems. We have contributed to the emerging idea that quorum sensing can stabilize cooperation through mechanisms of cheater restraint. We are also studying how cooperators and cheaters are involved in an evolutionary arms race where they continually improve their ability to compete with one another. Studies of bacteria offer a window into understanding cooperation in a broader sense and also the opportunity to observe the evolution of sociality in real time.