title: Staphylococcus epidermidis SrrAB regulates bacterial growth and biofilm formation differently under oxic and microaerobic conditions.
abstract: SrrAB expression in Staphylococcus epidermidis strain 1457 (SE1457) was upregulated during a shift from oxic to microaerobic conditions. An srrA deletion (ΔsrrA) mutant was constructed for studying the regulatory function of SrrAB. The deletion resulted in retarded growth and abolished biofilm formation both in vitro and in vivo and under both oxic and microaerobic conditions. Associated with the reduced biofilm formation, the ΔsrrA mutant produced much less polysaccharide intercellular adhesion (PIA) and showed decreased initial adherence capacity. Microarray analysis showed that the srrA mutation affected transcription of 230 genes under microaerobic conditions, and 51 genes under oxic conditions. Quantitative real-time PCR confirmed this observation and showed downregulation of genes involved in maintaining the electron transport chain by supporting cytochrome and quinol-oxidase assembly (e.g., qoxB and ctaA) and in anaerobic metabolism (e.g., pflBA and nrdD). In the ΔsrrA mutant, the expression of the biofilm formation-related gene icaR was upregulated under oxic conditions and downregulated under microaerobic conditions, whereas icaA was downregulated under both conditions. An electrophoretic mobility shift assay further revealed that phosphorylated SrrA bound to the promoter regions of icaR, icaA, qoxB, and pflBA, as well as its own promoter region. These findings demonstrate that in S. epidermidis SrrAB is an autoregulator and regulates biofilm formation in an ica-dependent manner. Under oxic conditions, SrrAB modulates electron transport chain activity by positively regulating qoxBACD transcription. Under microaerobic conditions, it regulates fermentation processes and DNA synthesis by modulating the expression of both the pfl operon and nrdDG.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China Integrated Laboratory of Pathogenic Biology, College of Preclinical Medicine, Dali University, Dali, China.
authors.forename: Youcong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China Department of Medical Parasitology, Wannan Medical College, Wuhu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Han
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Huayong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Genomic Research Laboratory, Service of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Patrice
authors.initials: P
authors.lastname: Francois
authors.affiliation: Genomic Research Laboratory, Service of Infectious Diseases, University of Geneva Hospitals, Geneva, Switzerland.
authors.forename: Adrien
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Integrated Laboratory of Pathogenic Biology, College of Preclinical Medicine, Dali University, Dali, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Microbial Genetics, University of Tübingen, Tübingen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China dqu@fudan.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development*; D004269:DNA, Bacterial / Q000378:metabolism; D004579:Electron Transport; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D020869:Gene Expression Profiling; D046228:Microarray Analysis; D010100:Oxygen / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D011135:Polysaccharides, Bacterial; D014157:Transcription Factors; D010100:Oxygen