Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

Capewell, P., Veitch, N.J. , Turner, C.M.R., Raper, J., Berriman, M., Hajduk, S.L. and MacLeod, A. (2011) Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by Trypanolytic factor 1. PLoS Neglected Tropical Diseases, 5(9), e1287. (doi: 10.1371/journal.pntd.0001287) (PMID:21909441) (PMCID:PMC3167774)

Abstract

<p><b>Background:</b> The three sub-species of <i>Trypanosoma brucei</i> are important pathogens of sub-Saharan Africa. <i>T. b. brucei</i> is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. <i>T. b. rhodesiense</i> and <i>T. b. gambiense</i> are able to resist lysis by TLF. There are two distinct sub-groups of <i>T. b. gambiense</i> that differ genetically and by human serum resistance phenotypes. Group 1 <i>T. b. gambiense</i> have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 <i>T. b. gambiense</i> are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (<i>HpHbR</i>)) gene. Here we investigate if this is also true in group 2 parasites.</p> <p><b>Methodology:</b> Isogenic resistant and sensitive group 2 <i>T. b. gambiense</i> were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the <i>HpHbR</i> gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to <i>T. b. brucei</i>. Both resistant and sensitive group 2, as well as group 1 <i>T. b. gambiense</i>, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.</p> <p><b>Conclusions:</b> Our data indicate that, despite group 1 <i>T. b. gambiense</i> avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 <i>T. b. gambiense</i> is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 <i>T. b. gambiense</i> variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of <i>HpHbR</i>. Thus there are differences in the mechanism of human serum resistance between <i>T. b. gambiense</i> groups 1 and 2.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLeod, Professor Annette and Veitch, Dr Nicola and Turner, Professor Charles and Capewell, Dr Paul
• Authors: Capewell, P., Veitch, N.J., Turner, C.M.R., Raper, J., Berriman, M., Hajduk, S.L., and MacLeod, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Neglected Tropical Diseases
• Publisher: Public Library of Science
• ISSN: 1935-2727
• ISSN (Online): 1935-2735
• Published Online: 06 September 2011
• Copyright Holders: Copyright © 2011 The Authors
• First Published: First published in PLoS Neglected Tropical Diseases 5(9):e1287
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher