IpgB1 and IpgB2, two homologous effectors secreted via the Mxi-Spa type III secretion apparatus, cooperate to mediate polarized cell invasion and inflammatory potential of Shigella flexenri

Microbes Infect. 2008 Mar;10(3):260-8. doi: 10.1016/j.micinf.2007.11.011. Epub 2007 Dec 8.


Type III secretion systems (T3SS) are present in many pathogenic gram-negative bacteria and mediate the translocation of bacterial effector proteins into host cells. Here, we report the phenotypic characterization of S. flexneri ipgB1 and ipgB2 mutants, in which the genes encoding the IpgB1 and IpgB2 effectors have been inactivated, either independently or simultaneously. Like IpgB1, we found that IpgB2 is secreted by the T3SS and its secretion requires the Spa15 chaperone. Upon infection of semi-confluent HeLa cells, the ipgB2 mutant exhibited the same invasive capacity as the wild-type strain and the ipgB1 mutant was 50% less invasive. Upon infection of polarised Caco2-cells, the ipgB2 mutant did not show a significant defect in invasion and the ipgB1 mutant was slightly more invasive than the wild-type strain. Entry of the ipgB1 ipgB2 mutant in polarized cells was reduced by 70% compared to the wild-type strain. Upon infection of the cornea in Guinea pigs, the ipgB2 mutant exhibited a wild-type phenotype, the ipgB1 mutant was hypervirulent and elicited a more pronounced proinflammatory response, while the ipgB1 ipgB2 mutant was highly attenuated. The attenuated phenotype of the ipgB1 ipgB2 mutant was confirmed using a murine pulmonary model of infection and histopathology and immunochemistry studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / metabolism*
  • Caco-2 Cells
  • Dysentery, Bacillary / microbiology*
  • Dysentery, Bacillary / pathology*
  • Female
  • HeLa Cells
  • Humans
  • Inflammation / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Point Mutation
  • Sequence Alignment
  • Shigella flexneri / metabolism*
  • Shigella flexneri / pathogenicity*
  • Virulence
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*


  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Molecular Chaperones
  • MxiD protein, Shigella
  • Spa15 protein, Shigella flexneri
  • IpgB1 protein, Shigella flexneri
  • IpgB2 protein, Shigella flexneri
  • rac1 GTP-Binding Protein