title: A Leishmania donovani gene that confers accelerated recovery from stationary phase growth arrest.
abstract: 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.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, Hamburg 20359, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hoyer
authors.forename: Dorothea
authors.initials: D
authors.lastname: Zander
authors.forename: Sandra
authors.initials: S
authors.lastname: Fleischer
authors.forename: Markus
authors.initials: M
authors.lastname: Schilhabel
authors.forename: Manfred
authors.initials: M
authors.lastname: Kroener
authors.forename: Mathias
authors.initials: M
authors.lastname: Platzer
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000818:Animals; D016054:DNA, Protozoan / Q000235:genetics; D005434:Flow Cytometry / Q000379:methods; D016193:G1 Phase / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics*; D007893:Leishmania donovani / Q000235:genetics* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D016196:S Phase / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D016054:DNA, Protozoan; C493157:GF1 protein, Leishmania donovani; D015800:Protozoan Proteins