REDUCED VIRULENCE OF RIFAMPICIN-RESISTANT MUTANTS OF FRANCISELLA-TULARENSIS

Rifampicin-resistant mutants of a live vaccine strain (LVS) of Francis ella tularensis were produced and screened for virulence in mice; 4 av irulent clones with intraperitoneal (ip) LD(50)s > 10(6) cfu, compared with 10(2) cfu for LVS, were characterized. Growth characteristics at 37 degrees C, surface envelope proteins, and lipopolysaccharide profi les of resistant mutants were identical to those of LVS. Polymerase ac tivity of the mutants was more resistant than the enzyme from LVS to t he inhibitory action of rifampicin. Growth rates for mutants and LVS w ere similar during the first 5 h at 42 degrees C, but viability of the mutants decreased to < 0.01% at 24 h. LVS and mutants differed in the ir ability to grow in vitro in host macrophages: LVS increased 580-fol d over 72 h; mutants increased 33-fold. After ip inoculation of the or ganisms into mice, increasing numbers of LVS from peritoneal cells wer e isolated; mutants decreased over 4 days.