A. Hubel et al., LEISHMANIA-MAJOR HSP100 IS REQUIRED CHIEFLY IN THE MAMMALIAN STAGE OFTHE PARASITE, Molecular and cellular biology, 17(10), 1997, pp. 5987-5995
In Leishmania major a 100-kDa heat shock protein, Hsp100, is abundant
in the intracellular amastigote stage which persists in the mammalian
host. A replacement of both clpB alleles which encode Hsp100 does not
affect promastigote viability under standard culture conditions but im
pairs thermotolerance in vitro. In experimental infections of BALB/c i
nbred mice, the lack of Hsp100 in the gene replacement mutants results
in a markedly delayed lesion development compared with that in infect
ions with wild-type L. major. Overexpression of exogenous clpB gene co
pies can partly restore virulence to the gene replacement mutants. Gen
etic-selection experiments also reveal a strong pressure for Hsp100 ex
pression in the mammalian stage. This requirement for Hsp100 was also
observed in in vitro infection experiments with mouse peritoneal macro
phages. These experiments indicated a role for Hsp100 during the devel
opment from the promastigote to the amastigote stage. Our results sugg
est an important role for this parasite heat shock protein during the
initial stages of a mammalian infection.