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Characterization of DalS, an ATP-binding cassette transporter for D-alanine, and its role in pathogenesis in Salmonella enterica

Lookup NU author(s): Dr Nhat Khai Bui, Professor Waldemar Vollmer

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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.


Publication metadata

Author(s): Osborne SE, Tuinema BR, Mok MCY, Lau PS, Bui NK, Tomljenovic-Berube AM, Vollmer W, Zhang K, Junop M, Coombes BK

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2012

Volume: 287

Issue: 19

Pages: 15242-15250

Print publication date: 14/03/2012

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M112.348227

DOI: 10.1074/jbc.M112.348227


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Funding

Funder referenceFunder name
Infrastructure Investment from the Canada Foundation for Innovation
Canada Research Chairs Program
MOP-82704Canadian Institutes of Health

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