The Brucella abortus host factor I (HF-I) protein contributes to stress resistance during stationary phase and is a major determinant of virulence inmice

Brucella abortus is a facultative intracellular pathogen that causes aborti on and infertility in domestic animals and a severe debilitating febrile il lness in humans. The mechanisms that this highly successful intracellular p athogen uses to adapt to, and survive within, the harsh intracellular envir onment of the host macrophage are presently unknown. Maintenance of the sta tionary phase growth state has been proposed to be critical for the virulen ce of several mammalian pathogens, but analysis of this relationship for th e brucellae has not been undertaken. In order to evaluate this relationship , we examined the in vitro and in vivo characteristics of an isogenic hfq m utant constructed from virulent Brucella abortus 2308. In Escherichia coli, the hfq gene product is an RNA-binding protein that participates in the re gulation of stationary phase stress resistance, at least partly by enhancin g translation of the stationary phase-specific sigma factor RpoS. As expect ed, the Brucella abortus hfq mutant, designated Hfq3, showed increased sens itivity to H2O2, and decreased survival under acidic conditions (pH 4.0), d uring stationary phase growth compared with 2308. Hfq3 was also less able t o withstand prolonged starvation than 2308. The Brucella abortus hfq mutant , unlike its parental strain 2308, fails to replicate in cultured murine ma crophages, and is rapidly cleared from the spleens and livers of experiment ally infected BALB/c mice. These findings suggest that the Brucella abortus hfq gene product makes an essential contribution to pathogenesis in mice, probably by allowing the brucellae to adapt appropriately to the harsh envi ronmental conditions encountered within the host macrophage.