Pirated Siderophores Promote Sporulation in Bacillus subtilis

In microbial communities, bacteria chemically and physically interact with one another. Some of these interactions are mediated by secreted specialized metabolites that act as either intraspecies or interspecies signals to alter gene expression and to change cell physiology. is a well-characterized soil microbe that can differentiate into multiple cell types, including metabolically dormant endospores. We were interested in identifying microbial interactions that affected sporulation in Using a fluorescent transcriptional reporter, we observed that coculturing with promoted sporulation gene expression via a secreted metabolite. To identify the active compound, we screened the Keio Collection and identified the sporulation-accelerating cue as the siderophore enterobactin. has multiple iron acquisition systems that are used to take up the produced siderophore bacillibactin, as well as to pirate exogenous siderophores such as enterobactin. While uses a single substrate binding protein (FeuA) to take up both bacillibactin and enterobactin, we discovered that it requires two distinct genes to sporulate in response to these siderophores (the esterase gene for bacillibactin and a putative esterase gene, , for enterobactin). In addition, we found that siderophores from a variety of other microbial species also promote sporulation in Our results thus demonstrate that siderophores can act not only as bacterial iron acquisition systems but also as interspecies cues that alter cellular development and accelerate sporulation in While much is known about the genetic regulation of sporulation, little is understood about how other bacteria influence this process. This work describes an interaction between and that accelerates sporulation in The interaction is mediated by the siderophore enterobactin; we show that other species' siderophores also promote sporulation gene expression in These results suggest that siderophores not only may supply bacteria with the mineral nutrient iron but also may play a role in bacterial interspecies signaling, providing a cue for sporulation. Siderophores are produced by many bacterial species and thus potentially play important roles in altering bacterial cell physiology in diverse environments.