An iron detection system determines bacterial swarming initiation and biofilm formation (original) (raw)

Abstract

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe 3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe 3+) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. Addition of Fe 3+ , or loss of ICDH-Coumarin due to pvc deletion results in prolonged RssAB signaling activation, leading to delayed swarming initiation and increased biofilm formation. We further show that ICDH-Coumarin is able to chelate Fe 3+ to switch off RssAB signaling, triggering swarming initiation and biofilm reduction. Our findings reveal a novel cellular system that senses iron levels to regulate bacterial surface lifestyle. Iron is essential for many cellular processes 1. While low iron bioavailability is a limiting factor for cell survival in hostile environments, excess iron within the cell is toxic due in part to the formation of hydroxyl radicals through Fenton reactions 2. Iron also serves as a stress signal that regulates microbial physiology, such as susceptibility to antibiotics 3. Competition between the host and pathogens for limited iron resources may determine infections outcome 4. Many homeostatic systems thus tightly control intracellular iron concentration in bacteria in order to allow adaptation to ever-changing environments 5-7. Swarming and biofilm formation are two typical multicellular behaviors of bacteria living on a surface 8. Bacteria within biofilms embedded in an extracellular matrix undergo cellular differentiation and may acquire resistance to environmental stress and host immune responses 9,10. On the other hand, swarming, which is observed in various bacterial species, represents a rapid, cell density-dependent, flagellum-driven movement of bacteria on a surface, and is closely associated with antibiotic resistance and production of virulence factors 11-15. Swarming is characterized by a non-motile lag phase and an active migration phase associated with metabolic

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