Bacterial-fungal interactions via redox-active "toxins"
Bacteria and fungi are the lungs of our planet. Despite their widespread interactions in nature and the clinical environment, little is known about the molecular mechanisms underlying these interactions and their potential impacts on human and ecosystem health. In particular, secreted redox-active molecules are increasingly recognized to mediate many types of interactions between bacteria and fungi, and thus can influence each organisms behavior and physiology under such a competitive and poly-microbial encounter. These redox-active molecules, e.g., bacteria-produced phenazines, fungi-produced gliotoxin and anthraquinones, are traditionally viewed as toxins to fend off their competitors via catalyzing the production of reactive oxygen species. However, more recent studies indicate 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 lead us to hypothesize that these secreted redox-active molecules may play diverse even opposite roles in bacterial-fungal interactions depending on a variety of factors, including their chemical structures, concentrations, environmental cues (such as pH, oxygen tension) and the ecological niches their producers and non-producers live in. For example, the same molecules that can trigger killing under one scenario might shift to benefit the development of the mixed species communities as a whole in response to the changes of environmental and physiological conditions. To test our hypothesis, we select to study interactions between two model organisms, Pseudomonas aeruginosa and Aspergillus fumigatus, the ubiquitous opportunistic bacterial and fungal pathogens, respectively, via secreted redox-active toxins. By combining physiological, genetic and metabolic profiling strategies, we hope to unravel the mechanisms that contribute to the friend or foe dynamic response in the small molecule-mediated mixed species interactions. The mechanistic nature of our approach will inevitably lead us into areas that are as relevant for medicine as for the environmental sciences and engineering.