The 5th Kinetoplastid Molecular Cell Biology meeting in Woods Hole MA kicks off on the 21st April, and I’m going to be speaking about some of the findings from our latest RNAi library screen.
Inhibition of Trypanosoma brucei cathepsin-L increases sensitivity to lysis by human serum.
Human serum (HS) is highly effective at killing non-human infective trypanosomes, such as T. b. brucei, T. congolense and T. vivax (though, unfortunately, T. b. gambiense and T. b. rhodesiense are unaffected, explaining their ability to cause devastating disease in humans).
From the work of several groups over the last two decades we know a huge amount about the mode of action of the HS trypanolytic factor (TLF; Vanhollebeke & Pays, 2010), as well as some of the ways that human infective African trypanosomes have evolved resistance (Stephens et al, 2012). However, although it’s known that TLF enters the parasite via the haptoglobin-haemoglobin receptor (HpHbR), the proteins that enable its transit to the lysosome are a mystery.
HS selection of the bloodstream form T. b. brucei RNAi library, and Illumina high thoughput sequencing of the remaining RNAi fragments, has identified proteins that likely influence the transit of TLF to the trypanosome lysosome and its action therein. This has revealed the first hints of a network of proteins, beyond the HpHbR, that influences the efficacy of TLF-mediated killing of African trypanosomes.