title: Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function.
abstract: Salmonella enterica serovar Typhimurium is a major cause of human gastroenteritis. Infection of epithelial monolayers by S. Typhimurium disrupts tight junctions that normally maintain the intestinal barrier and regulate cell polarity. Tight junction disruption is dependent upon the Salmonella pathogenicity island-1 (SPI-1) type 3 secretion system but the specific effectors involved have not been identified. In this study we demonstrate that SopB, SopE, SopE2 and SipA are the SPI-1-secreted effectors responsible for disruption of tight junction structure and function. Tight junction disruption by S. Typhimurium was prevented by inhibiting host protein geranylgeranylation but was not dependent on host protein synthesis or secretion of host-derived products. Unlike wild-type S. Typhimurium, DeltasopB, DeltasopE/E2, DeltasipA, or DeltasipA/sopB mutants, DeltasopB/E/E2 and DeltasipA/sopE/E2 mutants were unable to increase the permeability of polarized epithelial monolayers, did not disrupt the distribution or levels of ZO-1 and occludin, and did not alter cell polarity. These data suggest that SPI-1-secreted effectors utilize their ability to stimulate Rho family GTPases to disrupt tight junction structure and function.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Boyle
authors.forename: Nat F
authors.initials: NF
authors.lastname: Brown
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D018938:Caco-2 Cells; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000502:physiology / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000502:physiology*; D012486:Salmonella typhimurium / Q000472:pathogenicity* / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology / Q000648:ultrastructure*
chemical_list: D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; C103987:SopE protein, Salmonella; C436324:SopE2 protein, Salmonella typhimurium; C489224:SopB protein, Salmonella