Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these interactions is critical for understanding and modulating bacterial behavior in natural environments. While bacterial responses to foreign species are frequently characterized at the molecular and phenotypic level, the exogenous molecules that elicit these responses are understudied. Here, Zarrella and Khare outline a systematic strategy based on transcriptomics combined with genetic and biochemical screens of promoter–reporters to identify the molecules from one species that are sensed by another. The authors used this method to study interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus that are frequently found in coinfections. They discovered that P. aeruginosa senses diverse staphylococcal exoproducts including the metallophore staphylopine (StP), intermediate metabolites citrate and acetoin, and multiple molecules that modulate its iron starvation response. They observed that StP inhibits biofilm formation and that P. aeruginosa can utilize citrate and acetoin for growth, revealing that these interactions have both antagonistic and beneficial effects. The image shows an artistic rendering of a P. aeruginosa cell (green) amidst exoproducts (small cyan and blue spheres) secreted by surrounding S. aureus cells (dark blue).

Image Credit: Erina He, NIH Medical Arts