Friends or Foes: Bacterial-fungal interactions via redox-active toxins
Microbial interactions between bacteria and fungi exist in nearly every niche on the planet, such as lungs of cystic fibrosis patients, catheters, crop roots, soils, and concrete buildings. They are expected to have enormous impacts on our society, ranging from treating persistent microbial infections, to drug discovery, to biotechnology, to driving numerous biogeochemical cycles. Mirroring our human societies, bacteria and fungi living in multicellular communities (i.e., biofilms) are under constant negotiation or combat for resources in order to survive and thrive in a competitive and polymicrobial environment. Many of them deploy secreted small molecules to engage in such complex interactions, which can lead to the regulation of multicellular behavior in mixed-species communities. Despite their ubiquity, very little is known about the molecular mechanisms underlying these secreted molecules-mediated interactions, in particular, how they respond to environmental and ecological stimuli.
To address this, we have selected to study the interactions between Pseudomonas aeruginosa and Aspergillus fumigatus, the ubiquitous opportunistic bacterial and fungal pathogens, respectively, via secreted redox-active small molecules. These molecules, the so-called toxins (including phenazines and gliotoxin), have been traditionally viewed as chemical warfare to kill competing organisms via catalyzing the production of reactive oxygen species. However, more recent studies have indicated that it is hardly to be a one-sided story because they are often present at concentrations below their toxic thresholds, and interestingly, some are produced under oxygen-limited conditions. These have led us to hypothesize that the functions of these molecules are multifactorial, triggered by dynamic environmental processes (such as oxygen tension, pH, iron sources). Such functional strategies will tip the competitive balance in mixed-species biofilm communities by affecting social interactions and multicellular behavior. The outcome would be to maximize their chances of survival, either by sacrificing their competitive neighbors or by holding hands to overcome harsh times together. To test our hypothesis, we have designed a novel experimental system to study co-culture biofilm interactions between Pseudomonas aeruginosa and Aspergillus fumigatus. By combining genetic, physiological, and cutting-edge metabolic profiling strategies, we aim to decipher the complex regulatory and functional network of secreted molecules-mediated bacterial-fungal interactions.
REU-CBG Student(s) will work closely with motived and dedicated mentors, from whom learn various laboratory techniques from classical microbial culturing to cutting-edge analytical tools. Most importantly, this experience would help students build the vision of their own research/career future.