title: Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence.
abstract: The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal function and these proteins are considered integral parts of the secretion apparatus. Here we show that the espACD operon is not necessary for the secretion of EspB, another ESX-1 substrate, and this unimpeded secretion of EspB is associated with significant residual virulence. Upon further investigation, we found that purified EspB can facilitate M. tb virulence even in the absence of EsxA and EsxB, and may do so by binding the bioactive phospholipids phosphatidic acid and phosphatidylserine, both of which are potent bioactive molecules with prominent roles in eukaryotic cell signalling. Our findings provide new insights into the impact of the espACD operon on the ESX-1 apparatus and reveal a distinct virulence function for EspB with novel implications in M. tb-host interactions.
authors.affiliation: École Polytechnique Fédérale de Lausanne, Global Health Institute, Lausanne, Switzerland.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Jan
authors.initials: J
authors.lastname: Rybniker
authors.forename: Stefanie
authors.initials: S
authors.lastname: Boy-Röttger
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhar
authors.forename: Florence
authors.initials: F
authors.lastname: Pojer
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D058491:Bacterial Load; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D054884:Host-Pathogen Interactions; D006801:Humans; D009000:Monocytes / Q000382:microbiology / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D037521:Virulence Factors / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010743:Phospholipids; D037521:Virulence Factors