TABLE 2.

Virulence factors encoded on the S. flexneri virulence plasmid

EffectorBiochemical activityHost cell target(s)Virulence function and/or phenotypeReference(s)b
IpaAVinculin activationVinculin, β1-integrins, Rho signalingEfficient invasion, actin cytoskeleton rearrangements, disassembly of cell-matrix adherence52, 96, 121, 311
IpaBMembrane fusionCholesterol, CD44, caspase-1Control of type III secretion, translocon formation, phagosome escape, macrophage apoptosis23, 36, 103, 109, 114, 170
IpaCActin polymerizationActin, β-cateninTranslocon formation, filopodium formation, phagosome escape, disruption of EC tight junctions23, 100, 171, 312
IpaDControl of type III secretion, membrane insertion of translocon68, 170, 317
IpaH7.8Efficient phagosome escape73
IpaH9.8E3 ubiquitin ligaseSplicing factor U2AF, MAPK kinaseHost cell transcriptome modulation, reduction of inflammation197, 236, 309
IcsAa (VirG)N-WASP, vinculinRecruitment of actin-nucleating complex required for actin-based motility and intercellular spread22, 84, 296, 298
IcsBCamouflage of IcsA to prevent autophagic recognition7, 194, 195
IcsPaSerine proteaseCleavage of IcsA, modulation of actin-based motility63, 278
IpgB1RhoG mimicryELMO proteinInduction of Rac1-dependent membrane ruffling12, 99, 196
IpgB2RhoA mimicryRhoA ligandsInduction of actin stress fiber-dependent membrane ruffling12
IpgDPhosphoinositide 4-phosphatasePhosphatidylinositol 4,5-bisphosphateFacilitation of entry, promotion of host cell survival187, 188, 212
OspBT3SS substrate, unknown function258
OspC1Nucleus and cytoplasmInduction of PMN migration344
OspD1T3SS substrate, unknown function in host cells, antiactivator of MxiE207
OspE2Focal contactsMaintenance of EC morphology, efficient intercellular spread173
OspFPhosphothreonine lyaseMAPKs Erk and p38Inhibition of histone phosphorylation and NF-κB-dependent gene expression, reduction of PMN recruitment14, 137, 151, 344
OspGProtein kinase, ubiquitination inhibitorUbiquitin-conjugating enzymesDownregulation of NF-κB activation, reduction of inflammation131
PhoN2aApyraseUnipolar localization of IcsA258
SepAaSerine proteasePromotion of intestinal tissue invasion and destruction20
VirACysteine proteaseα-TubulinFacilitation of entry and intracellular motility by degradation of microtubules338, 339
  • a These proteins are not substrates of the Mxi-Spa T3SS.

  • b For the sake of clarity, only the most relevant references are cited.