title: The passenger-associated transport repeat promotes virulence factor secretion efficiency and delineates a distinct autotransporter subtype.
abstract: Autotransporters are a superfamily of virulence factors secreted by Gram negative bacteria. They are comprised of an N-terminal passenger domain that is translocated across the outer membrane and a C-terminal domain that inserts into the outer membrane forming a β-barrel anchor. It is still poorly understood how the passenger is efficiently translocated in the absence of external energy inputs. Several mechanisms have been proposed in solution of this problem, yet due to the vast diversity of size, sequence and function of the passenger, it is not clear how widely these mechanisms are employed. In this study we functionally characterize a conserved repeat found in many passengers that we designate the Passenger-associated Transport Repeat (PATR). Using the autotransporter IcsA from the enteropathogen Shigella flexneri, we identified conserved PATR residues that are required for efficient export of the passenger during growth and infection. Furthermore, PATR-containing autotransporters are significantly larger than non-PATR autotransporters, with PATR copy number correlating with passenger size. We also show that PATR-containing autotransporters delineate a subgroup that associates with specific virulence traits and architectures. These results advance our understanding of autotransporter composition and indicate that an additional transport mechanism is important for thousands of these proteins.
authors: Department of Molecular and Cellular Biology, School of Biological Sciences, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors: Matthew Thomas
authors: MT
authors: Doyle
authors: Department of Molecular and Cellular Biology, School of Biological Sciences, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors: Elizabeth Ngoc Hoa
authors: EN
authors: Tran
authors: Department of Molecular and Cellular Biology, School of Biological Sciences, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors: Renato
authors: R
authors: Morona
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D030541:Databases, Genetic; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D021381:Protein Transport; D000069320:Type V Secretion Systems / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D000069320:Type V Secretion Systems; D037521:Virulence Factors