Let me tell you about our newest preprint – a story of heat shock and prenylation in Plasmodium falciparum!
biorxiv.org/content/10.110…
[Thread]
Most people with malaria get fever - how do malaria parasites survive that stress? /1
First of all, P. falciparum has a ton of heat shock proteins. In particular the DnaJ/Hsp40 family is very expanded – there are 49 Hsp40 family members in P. falciparum!! /2
Reviewed here: mdpi.com/2218-273X/9/7/…
We have previously found that one of these Hsp40s in Plasmodium is farnesylated – that is, modified by a 15-carbon isoprenyl group. We call it HSP40 and it is the canonical Hsp40 in malaria parasites. /3
more on the "prenylome" of malaria parasites: nature.com/articles/srep3…
Guess what? If you inhibit farnesylation OR total synthesis of #isoprenoids – parasites can’t tolerate temperature changes any more. Inhibitors + heat/cold shock = dead parasites! 🦠+🔥=💀/4
So, these inhibitors are likely to be even better in sick people than they are in vitro (and they’re already pretty good).. and probably block mosquito transmission (a cold shock).
Many more details in the preprint – looking forward to feedback! /fin
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