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 adherence 52, 96, 121, 311
IpaBMembrane fusionCholesterol, CD44, caspase-1Control of type III secretion, translocon formation, phagosome escape, macrophage apoptosis 23, 36, 103, 109, 114, 170
IpaCActin polymerizationActin, β-cateninTranslocon formation, filopodium formation, phagosome escape, disruption of EC tight junctions 23, 100, 171, 312
IpaDControl of type III secretion, membrane insertion of translocon 68, 170, 317
IpaH7.8Efficient phagosome escape 73
IpaH9.8E3 ubiquitin ligaseSplicing factor U2AF, MAPK kinaseHost cell transcriptome modulation, reduction of inflammation 197, 236, 309
IcsAa (VirG)N-WASP, vinculinRecruitment of actin-nucleating complex required for actin-based motility and intercellular spread 22, 84, 296, 298
IcsBCamouflage of IcsA to prevent autophagic recognition 7, 194, 195
IcsPaSerine proteaseCleavage of IcsA, modulation of actin-based motility 63, 278
IpgB1RhoG mimicryELMO proteinInduction of Rac1-dependent membrane ruffling 12, 99, 196
IpgB2RhoA mimicryRhoA ligandsInduction of actin stress fiber-dependent membrane ruffling 12
IpgDPhosphoinositide 4-phosphatasePhosphatidylinositol 4,5-bisphosphateFacilitation of entry, promotion of host cell survival 187, 188, 212
OspBT3SS substrate, unknown function 258
OspC1Nucleus and cytoplasmInduction of PMN migration 344
OspD1T3SS substrate, unknown function in host cells, antiactivator of MxiE 207
OspE2Focal contactsMaintenance of EC morphology, efficient intercellular spread 173
OspFPhosphothreonine lyaseMAPKs Erk and p38Inhibition of histone phosphorylation and NF-κB-dependent gene expression, reduction of PMN recruitment 14, 137, 151, 344
OspGProtein kinase, ubiquitination inhibitorUbiquitin-conjugating enzymesDownregulation of NF-κB activation, reduction of inflammation 131
PhoN2aApyraseUnipolar localization of IcsA 258
SepAaSerine proteasePromotion of intestinal tissue invasion and destruction 20
VirACysteine proteaseα-TubulinFacilitation of entry and intracellular motility by degradation of microtubules 338, 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.