Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts

Upasna Gaur; Melissa Showalter; Suzanne Hickerson; Rahul Dalvi; Salvatore J Turco; Mary E Wilson; Stephen M Beverley

doi:10.1016/j.exppara.2009.03.014

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Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts

Journal article

Peer reviewed

Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts

Upasna Gaur, Melissa Showalter, Suzanne Hickerson, Rahul Dalvi, Salvatore J Turco, Mary E Wilson and Stephen M Beverley

Experimental parasitology, Vol.122(3), pp.182-191

07/2009

DOI: 10.1016/j.exppara.2009.03.014

PMCID: PMC2720449

PMID: 19328787

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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−Leishmaniadonovani 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.

glycosylinositol phospholipids

LPG

PPG

RP-10

phosphoglycan

proteophosphoglycan

lipophosphoglycan

macrophage growth medium with RPMI and 10% FCS

GIPL

Details

Title: Subtitle: Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts
Creators: Upasna Gaur - Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, SW34-GH, 200 Hawkins Dr., Iowa City, IA 52242, USA
Melissa Showalter - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Suzanne Hickerson - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Rahul Dalvi - Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, SW34-GH, 200 Hawkins Dr., Iowa City, IA 52242, USA
Salvatore J Turco - Department of Biochemistry, University of Kentucky Medical Center, College of Medicine, Lexington 40536, USA
Mary E Wilson - Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, SW34-GH, 200 Hawkins Dr., Iowa City, IA 52242, USA
Stephen M Beverley - Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
Resource Type: Journal article
Publication Details: Experimental parasitology, Vol.122(3), pp.182-191
DOI: 10.1016/j.exppara.2009.03.014
PMID: 19328787
PMCID: PMC2720449
NLM abbreviation: Exp Parasitol
ISSN: 0014-4894
eISSN: 1090-2449
Publisher: Elsevier BV
Language: English
Date published: 07/2009
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001142502771

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