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dc.contributor.authorDuMont, Ashley L
dc.contributor.authorYoong, Pauline
dc.contributor.authorLiu, Xiang
dc.contributor.authorDay, Christopher J
dc.contributor.authorChumbler, Nicole M
dc.contributor.authorJames, David BA
dc.contributor.authorAlonzo, Francis
dc.contributor.authorBode, Nadine J
dc.contributor.authorLacy, D Borden
dc.contributor.authorJennings, Michael P
dc.contributor.authorTorres, Victor J
dc.date.accessioned2017-10-30T12:31:43Z
dc.date.available2017-10-30T12:31:43Z
dc.date.issued2014
dc.identifier.issn0019-9567
dc.identifier.doi10.1128/IAI.01444-13
dc.identifier.urihttp://hdl.handle.net/10072/66795
dc.description.abstractThe bicomponent leukotoxins produced by Staphylococcus aureus kill host immune cells through osmotic lysis by forming ??-barrel pores in the host plasma membrane. The current model for bicomponent pore formation proposes that octameric pores, comprised of two separate secreted polypeptides (S and F subunits), are assembled from water-soluble monomers in the extracellular milieu and multimerize on target cell membranes. However, it has yet to be determined if all staphylococcal bicom- ponent leukotoxin family members exhibit these properties. In this study, we report that leukocidin A/B (LukAB), the most di- vergent member of the leukotoxin family, exists as a heterodimer in solution rather than two separate monomeric subunits. No- tably, this property was found to be associated with enhanced toxin activity. LukAB also differs from the other bicomponent leukotoxins in that the S subunit (LukA) contains 33- and 10-amino-acid extensions at the N and C termini, respectively. Trun- cation mutagenesis revealed that deletion of the N terminus resulted in a modest increase in LukAB cytotoxicity, whereas the deletion of the C terminus rendered the toxin inactive. Within the C terminus of LukA, we identified a glutamic acid at position 323 that is critical for LukAB cytotoxicity. Furthermore, we discovered that this residue is conserved and required for the inter- action between LukAB and its cellular target CD11b. Altogether, these findings provide an in-depth analysis of how LukAB tar- gets neutrophils and identify novel targets suitable for the rational design of anti-LukAB inhibitors.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1268
dc.relation.ispartofpageto1276
dc.relation.ispartofissue3
dc.relation.ispartofjournalInfection and Immunity
dc.relation.ispartofvolume82
dc.rights.retentionY
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchAgricultural, veterinary and food sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchMedical bacteriology
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode30
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320701
dc.titleIdentification of a crucial residue required for Staphylococcus aureus LukAB cytotoxicity and receptor recognition
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2014 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorDay, Christopher J.


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