title: An iron detection system determines bacterial swarming initiation and biofilm formation.
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-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe3+) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. Addition of Fe3+, 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 Fe3+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.
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Tseng
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Tsung-Ru
authors.initials: TR
authors.lastname: Wu
authors.affiliation: Department of Respiratory Therapy, Fu Jen University, New Taipei City, Taiwan, Republic of China.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
authors.forename: Ting-Shu
authors.initials: TS
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
authors.forename: Jang-Jih
authors.initials: JJ
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Jim-Tong
authors.initials: JT
authors.lastname: Horng
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Jan
authors.initials: J
authors.lastname: Martel
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China.|Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.|Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, United States of America.|Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City, Taiwan, Republic of China.
authors.forename: John D
authors.initials: JD
authors.lastname: Young
mesh_terms: D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018441:Biofilms; D003374:Coumarins / Q000378:metabolism; D005407:Flagella / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D012706:Serratia marcescens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C532942:2-isocyano-6,7-dihydroxycoumarin; D001426:Bacterial Proteins; D003374:Coumarins; D007501:Iron