Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9536-41. Epub 2003 Jul 17.

The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts.

Author information

  • 1Department of Molecular Microbiology, Washington University Medical School, St. Louis, MO 63110, USA.


The abundant cell surface glycolipid lipophosphoglycan (LPG) was implicated in many steps of the Leishmania infectious cycle by biochemical tests. The presence of other abundant surface or secreted glycoconjugates sharing LPG domains, however, has led to uncertainty about the relative contribution of LPG in vivo. Here we used an Leishmania major lpg1- mutant, which lacks LPG alone and shows attenuated virulence, to dissect the role of LPG in the establishment of macrophage infections in vivo. lpg1- was highly susceptible to human complement, had lost the ability to inhibit phagolysosomal fusion transiently, and was oxidant sensitive. Studies of mouse mutants defective in relevant defense mechanisms confirmed the role of LPG in oxidant resistance but called into question the importance of transient inhibition of phagolysosomal fusion for Leishmania macrophage survival. Moreover, the limited lytic activity of mouse complement appears to be an ineffective pathogen defense mechanism in vitro and in vivo, unlike human hosts. In contrast, lpg1- parasites bound C3b and resisted low pH and proteases normally, entered macrophages efficiently and silently, and continued to inhibit host-signaling pathways. These studies illustrate the value of mechanistic approaches focusing on both parasite and host defense pathways in dissecting the specific biological roles of complex virulence factors such as LPG.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 5.
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk