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Identification of T rypanosoma brucei components involved in trypanolysis by normal human serum
Author(s) -
Lecordier Laurence,
Uzureau Pierrick,
Tebabi Patricia,
PérezMorga David,
Nolan Derek,
Schumann Burkard Gabriela,
Roditi Isabel,
Pays Etienne
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12783
Subject(s) - biology , identification (biology) , computational biology , trypanosoma brucei , genetics , gene , ecology
Summary Normal human serum ( NHS ) confers human resistance to infection by the parasite T rypanosoma brucei owing to the trypanolytic activity of apolipoprotein L 1 ( APOL1 ), present in two serum complexes termed Trypanolytic Factors ( TLF ‐1 and ‐2). In order to identify parasite components involved in the intracellular trafficking and activity of TLFs , an inducible RNA interference ( RNAi ) genomic DNA library constructed in bloodstream form T . brucei was subjected to RNAi induction and selection for resistant parasites under NHS conditions favouring either TLF ‐1 or TLF ‐2 uptake. While TLF ‐1 conditions readily selected the haptoglobin‐haemoglobin ( HP ‐ HB ) surface receptor TbHpHbR as expected, given its known ability to bind TLF ‐1, under TLF ‐2 conditions no specific receptor for TLF ‐2 was identified. Instead, the screen allowed the identification of five distinct factors expected to be involved in the assembly of the vacuolar proton pump V ‐ ATPase and consecutive endosomal acidification. These data confirm that lowering the pH during endocytosis is required for APOL 1 toxic activity.