9zrs | pdb_00009zrs
Shigella flexneri type III secretion system (T3SS) protein IpaD bound to hemolysis blocking Fab D02-F2 and hemolysis enhancing Fab D02-E4
Structural highlights
FunctionIPAD_SHIFL Required for bacterial invasion of host cells. Controls IpaB and IpaC secretion, and the efficiency with which they are physically inserted into target cell membranes. These proteins are exported via TTSS to form a pore in the host membrane that allows the translocation of the other effectors into the host cytoplasm. Along with IpaB, is essential for both blocking secretion through the Mxi/Spa translocon in the absence of a secretion-inducing signal, and for controlling the level of secretion in the presence of this signal.[1] [2] Publication Abstract from PubMedThere is currently no approved vaccine for Shigella spp., a leading cause of diarrhea with increasing rates of antimicrobial resistance. Shigella vaccine development is complicated in part by an incomplete understanding of the structural and molecular determinants of immunity. To address this, we isolated monoclonal antibodies against candidate Shigella vaccine antigens using samples from a Shigella flexneri outbreak in a nonhuman primate (NHP) research facility. We found that antibodies targeting the Shigella O-antigen can undergo substantial affinity maturation (>10%) to acquire broad cross-reactivity across S. flexneri serotypes. We also found that the virulence-associated type III secretion system (T3SS) proteins IpaD and IpaB elicit moderate T cell and robust antibody responses. T3SS antibodies could either inhibit or enhance bacterial virulence in vitro and differed in vivo depending on their epitope specificity. Collectively, these findings provide insights into protective and deleterious immune responses against Shigella that directly inform vaccine immunogen design. Multifunctional antibody responses from a primate Shigella outbreak inform vaccine design.,Gallant RM, Savarino P, Pulido S, Gilman MSA, Lu T, Hayes J, Xerri NL, Williams T, Ochoa MA, Dietz Z, Peterson E, Scott T, Hartmann F, Baker SG, Kaminski RW, Sok D, Kruse AC, Picking W, Capuano SV, Schmidt HR Sci Transl Med. 2026 Sep 2;18(865):eaef7084. doi: 10.1126/scitranslmed.aef7084. , Epub 2026 Sep 2. PMID:42685149[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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