title: Characterization of DalS, an ATP-binding cassette transporter for D-alanine, and its role in pathogenesis in Salmonella enterica.
abstract: Expansion into new host niches requires bacterial pathogens to adapt to changes in nutrient availability and to evade an arsenal of host defenses. Horizontal acquisition of Salmonella Pathogenicity Island (SPI)-2 permitted the expansion of Salmonella enterica serovar Typhimurium into the intracellular environment of host cells by allowing it to deliver bacterial effector proteins across the phagosome membrane. This is facilitated by the SsrA-SsrB two-component regulatory system and a type III secretion system encoded within SPI-2. SPI-2 acquisition was followed by evolution of existing regulatory DNA, creating an expanded SsrB regulon involved in intracellular fitness and host infection. Here, we identified an SsrB-regulated operon comprising an ABC transporter in Salmonella. Biochemical and structural studies determined that the periplasmic solute-binding component, STM1633/DalS, transports D-alanine and that DalS is required for intracellular survival of the bacteria and for fitness in an animal host. This work exemplifies the role of nutrient exchange at the host-pathogen interface as a critical determinant of disease outcome.
authors.affiliation: Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, L8N 3Z5, Canada.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Osborne
authors.forename: Brian R
authors.initials: BR
authors.lastname: Tuinema
authors.forename: Mac C Y
authors.initials: MC
authors.lastname: Mok
authors.forename: Pui Sai
authors.initials: PS
authors.lastname: Lau
authors.forename: Nhat Khai
authors.initials: NK
authors.lastname: Bui
authors.forename: Ana M
authors.initials: AM
authors.lastname: Tomljenovic-Berube
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Murray
authors.initials: M
authors.lastname: Junop
authors.forename: Brian K
authors.initials: BK
authors.lastname: Coombes
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000409:Alanine / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D033903:Periplasmic Proteins; C119761:SsrB protein, Salmonella typhimurium; D014157:Transcription Factors; D037521:Virulence Factors; D000409:Alanine