title: Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts.
abstract: Surface phosophoglycans such as lipophosphoglycan (LPG) or proteophosphoglycan (PPG) and glycosylinositol phospholipids (GIPLs) modulate essential interactions between Leishmania and mammalian macrophages. Phosphoglycan synthesis depends on the Golgi GDP-mannose transporter encoded by LPG2. LPG2-null (lpg2(-)) Leishmania major cannot establish macrophage infections or induce acute pathology, whereas lpg2(-)Leishmania mexicana retain virulence. lpg2(-)Leishmania donovani has been reported to survive poorly in cultured macrophages but in vivo survival has not been explored. Herein we discovered that, similar to lpg2(-)L. major, lpg2(-)L. donovani promastigotes exhibited diminished virulence in mice, but persisted at consistently low levels. lpg2(-)L. donovani promastigotes could not establish infection in macrophages and could not transiently inhibit phagolysosomal fusion. Furthermore, lpg2(-) promastigotes of L. major, L. donovani and L. mexicana were highly susceptible to complement-mediated lysis. We conclude that phosphoglycan assembly and expression mediated by L. donovani LPG2 are important for promastigote and amastigote virulence, unlike L. mexicana but similar to L. major.
authors.affiliation: Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, 200 Hawkins Drive, Iowa City, IA 52242, USA.
authors.forename: Upasna
authors.initials: U
authors.lastname: Gaur
authors.forename: Melissa
authors.initials: M
authors.lastname: Showalter
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hickerson
authors.forename: Rahul
authors.initials: R
authors.lastname: Dalvi
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Turco
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley