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Absence of O antigen suppresses Shigella flexneri IcsA autochaperone region mutations

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dc.contributor.authorTeh, M.
dc.contributor.authorTran, N.
dc.contributor.authorMorona, R.
dc.date.issued2012
dc.description.abstractThe Shigella flexneri IcsA (VirG) protein is a polarly distributed autotransporter protein. IcsA functions as a virulence factor by interacting with the host actin regulatory protein N-WASP, which in turn activates the Arp2/3 complex, initiating actin polymerization. Formation of F-actin comet tails allows bacterial cell-to-cell spreading. Although various accessory proteins such as periplasmic chaperones and the β-barrel assembly machine (BAM) complex have been shown to be involved in the export of IcsA, the IcsA translocation mechanism remains to be fully elucidated. A putative autochaperone (AC) region (amino acids 634–735) located at the C-terminal end of the IcsA passenger domain, which forms part of the self-associating autotransporter (SAAT) domain, has been suggested to be required for IcsA biogenesis, as well as for N-WASP recruitment, based on mutagenesis studies. IcsAi proteins with linker insertion mutations within the AC region have a significant reduction in production and are defective in N-WASP recruitment when expressed in smooth LPS (S-LPS) S. flexneri. In this study, we have found that the LPS O antigen plays a role in IcsAi production based on the use of an rmlD (rfbD) mutant having rough LPS (R-LPS) and a novel assay in which O antigen is depleted using tunicamycin treatment and then regenerated. In addition, we have identified a new N-WASP binding/interaction site within the IcsA AC region.
dc.description.statementofresponsibilityMin Yan Teh, Elizabeth Ngoc Hoa Tran and Renato Morona
dc.identifier.citationMicrobiology, 2012; 158(11):2835-2850
dc.identifier.doi10.1099/mic.0.062471-0
dc.identifier.issn1350-0872
dc.identifier.issn1465-2080
dc.identifier.orcidTran, N. [0000-0003-1644-2287]
dc.identifier.orcidMorona, R. [0000-0001-7009-7440]
dc.identifier.urihttp://hdl.handle.net/2440/74744
dc.language.isoen
dc.publisherSoc General Microbiology
dc.relation.isreplacedby2440/89851
dc.relation.isreplacedbyhttp://hdl.handle.net/2440/89851
dc.rights© 2012 SGM
dc.source.urihttps://doi.org/10.1099/mic.0.062471-0
dc.subjectHela Cells
dc.subjectHumans
dc.subjectShigella flexneri
dc.subjectDysentery, Bacillary
dc.subjectO Antigens
dc.subjectBacterial Proteins
dc.subjectDNA-Binding Proteins
dc.subjectTranscription Factors
dc.subjectDown-Regulation
dc.subjectAmino Acid Motifs
dc.subjectProtein Binding
dc.subjectProtein Transport
dc.subjectMutation
dc.subjectWiskott-Aldrich Syndrome Protein, Neuronal
dc.subjectPromoter Regions, Genetic
dc.titleAbsence of O antigen suppresses Shigella flexneri IcsA autochaperone region mutations
dc.typeJournal article
pubs.publication-statusPublished

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