title: Nucleoid-associated protein HU controls three regulons that coordinate virulence, response to stress and general physiology in Salmonella enterica serovar Typhimurium.
abstract: The role of the HU nucleoid-associated proteins in gene regulation was examined in Salmonella enterica serovar Typhimurium. The dimeric HU protein consists of different combinations of its α and β subunits. Transcriptomic analysis was performed with cultures growing at 37 °C at 1, 4 and 6 h after inoculation with mutants that lack combinations of HU α and HU β. Distinct but overlapping patterns of gene expression were detected at each time point for each of the three mutants, revealing not one but three regulons of genes controlled by the HU proteins. Mutations in the hup genes altered the expression of regulatory and structural genes in both the SPI1 and SPI2 pathogenicity islands. The hupA hupB double mutant was defective in invasion of epithelial cell lines and in its ability to survive in macrophages. The double mutant also had defective swarming activity and a competitive fitness disadvantage compared with the wild-type. In contrast, inactivation of just the hupB gene resulted in increased fitness and correlated with the upregulation of members of the RpoS regulon in exponential-phase cultures. Our data show that HU coordinates the expression of genes involved in central metabolism and virulence and contributes to the success of S. enterica as a pathogen.
authors.affiliation: Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mangan
authors.affiliation: Department of Molecular Microbiology, Institute for Food Research, Colney, Norwich NR4 7UA, UK.
authors.forename: Sacha
authors.initials: S
authors.lastname: Lucchini
authors.affiliation: Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
authors.forename: Tadhg
authors.initials: T
authors.lastname: Ó Cróinín
authors.affiliation: Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Fitzgerald
authors.affiliation: Department of Molecular Microbiology, Institute for Food Research, Colney, Norwich NR4 7UA, UK.|Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
authors.forename: Jay C D
authors.initials: JCD
authors.lastname: Hinton
authors.affiliation: Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dorman
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D044404:Genomic Islands; D008124:Locomotion; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D012486:Salmonella typhimurium / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological; D013696:Temperature; D013997:Time Factors; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D021122:Protein Subunits; C040330:histone-like protein HU, bacteria