A Leishmania donovani gene that confers accelerated recovery from stationary phase growth arrest

We have isolated a gene, LdGF1, from the protozoan parasite Leishmania donovani. Overexpression of this gene confers a strong selective advantage in liquid culture after stationary phase growth arrest. We could show that recombinant L. donovani or Leishmania major, when overexpressing LdGF1, recover faster from a stationary phase growth arrest than control parasite strains. While no advantage of LdGF1 overexpression could be observed in log phase cultures or after a hydroxyurea-induced S-phase growth arrest, recovery from a cell cycle arrest due to serum deprivation was faster in LdGF1-overexpressing strains. This was found to be due to an accelerated release from a G(1) cell cycle arrest. By contrast, in a BALB/c mouse infection system, overexpression of LdGF1 in L. major resulted in reduced virulence. We conclude that increased levels of LdGF1 are beneficiary during recovery from G(1) cell cycle arrest, but pose a disadvantage inside a mammalian host. These results are discussed in the context of the observed loss of virulence during in vitro passage of Leishmania parasites.