title: Functional relatedness in the Inv/Mxi-Spa type III secretion system family.
abstract: Type III Secretion Systems (T3SSs) are structurally conserved nanomachines that span the inner and outer bacterial membranes, and via a protruding needle complex contact host cell membranes and deliver type III effector proteins. T3SS are phylogenetically divided into several families based on structural basal body components. Here we have studied the evolutionary and functional conservation of four T3SS proteins from the Inv/Mxi-Spa family: a cytosolic chaperone, two hydrophobic translocators that form a plasma membrane-integral pore, and the hydrophilic 'tip complex' translocator that connects the T3SS needle to the translocon pore. Salmonella enterica serovar Typhimurium (S. Typhimurium), a common cause of food-borne gastroenteritis, possesses two T3SSs, one belonging to the Inv/Mxi-Spa family. We used invasion-deficient S. Typhimurium mutants as surrogates for expression of translocator orthologs identified from an extensive phylogenetic analysis, and type III effector translocation and host cell invasion as a readout for complementation efficiency, and identified several Inv/Mxi-Spa orthologs that can functionally substitute for the S. Typhimurium chaperone and translocator proteins. Functional complementation correlates with amino acid sequence identity between orthologs, but varies considerably between the four proteins. This is the first in-depth survey of the functional interchangeability of Inv/Mxi-Spa T3SS proteins acting directly at the host-pathogen interface.
authors.affiliation: Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Klein
authors.affiliation: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Biren M
authors.initials: BM
authors.lastname: Dave
authors.affiliation: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Amogelang R
authors.initials: AR
authors.lastname: Raphenya
authors.affiliation: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: McArthur
authors.affiliation: Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164, USA.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Knodler
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000378:metabolism*; D000069296:Type III Secretion Systems / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C107188:SspD protein, Salmonella typhimurium; D000069296:Type III Secretion Systems; C094579:invasion protein B, Salmonella typhimurium