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Ricin-resistant mutants of Leishmania major which express modified lipophosphoglycan remain infective for mice

Published online by Cambridge University Press:  06 April 2009

R. Cappai ,
L. Morris ,
T. Aebischer ,
A. Bacic ,
J. M. Curtis ,
M. Kelleher ,
K. S. McLeod ,
S. F. Moody ,
A. H. Osborn  and
E. Handman
R. Cappai
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
L. Morris
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
T. Aebischer
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
A. Bacic
Affiliation:
Plant Cell Biology Centre, School of Botany, University of Melbourne, Parkville 3052, Australia
J. M. Curtis
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
M. Kelleher
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
K. S. McLeod
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
S. F. Moody
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
A. H. Osborn
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
E. Handman
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia
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Summary

Glycosylation variants of the virulent Leishmania major clone VI21 were generated by mutagenesis with N-methyl-N-nitroso-N-nitroguanidine and selected using the galactose-specific lectin Ricinus communis II (RCA II). Three mutants, 4B9, 1D1 and 1C12, which failed to bind RCA II, were found to have an altered expression of lipophosphoglycan (LPG), a molecule implicated in the attachment to host macrophages and survival within the phagolysosome. There were differences in the antigenicity, molecular weight and localization of LPG from mutant parasites as compared to V121. Expression of gp63, a surface molecule also implicated in attachment to macrophages, was unaltered. All 3 mutants caused disease when injected into genetically susceptible BALB/c mice but lesions developed at a much slower rate than those caused by the virulent V121 clone. This slow rate of lesion development did not correlate with promastigotes' ability to invade macrophages in vitro. Karyotype analysis showed that there was a reduction in the size of chromosome band number 2 in all 3 mutants. The differences in LPG and chromosome band 2 were retained by mutant clones following passage through mice, suggesting that these phenotypes are stable. Although the mutant parasites were infective and caused lesions, the changed structure of the LPG appeared to influence the virulence of the parasites.

Keywords

Leishmaniavirulencelipophosphoglycanmutant
Type
Research Article
Information
Parasitology , Volume 108 , Issue 4 , May 1994 , pp. 397 - 405
Copyright
Copyright © Cambridge University Press 1994

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