title: Pirated Siderophores Promote Sporulation in Bacillus subtilis.
abstract: 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.Bacillus subtilisis 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 inB. subtilisUsing a fluorescent transcriptional reporter, we observed that coculturingB. subtiliswithEscherichia colipromoted sporulation gene expression via a secreted metabolite. To identify the active compound, we screened theE. coliKeio Collection and identified the sporulation-accelerating cue as the siderophore enterobactin.B. subtilishas multiple iron acquisition systems that are used to take up theB. subtilis-produced siderophore bacillibactin, as well as to pirate exogenous siderophores such as enterobactin. WhileB. subtilisuses 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 genebesAfor bacillibactin and a putative esterase gene,ybbA, for enterobactin). In addition, we found that siderophores from a variety of other microbial species also promote sporulation inB. subtilisOur 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 inB. subtilisIMPORTANCEWhile much is known about the genetic regulation ofBacillus subtilissporulation, little is understood about how other bacteria influence this process. This work describes an interaction betweenEscherichia coliandB. subtilisthat accelerates sporulation inB. subtilisThe interaction is mediated by theE. colisiderophore enterobactin; we show that other species' siderophores also promote sporulation gene expression inB. subtilisThese 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.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Grandchamp
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Lews
authors.initials: L
authors.lastname: Caro
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA eshank@unc.edu.|Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Curriculum of Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Elizabeth A
authors.identifier: http://orcid.org/0000-0002-4804-1966
authors.initials: EA
authors.lastname: Shank
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004758:Enterobactin / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D017262:Siderophores / Q000378:metabolism*; D013171:Spores, Bacterial / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D009842:Oligopeptides; D017262:Siderophores; C430721:bacillibactin; D004758:Enterobactin; D007501:Iron
keywords: Bacillus subtilis; Escherichia coli; cell-cell interaction; coculture; secondary metabolites; siderophores; specialized metabolites; sporulation