ABSTRACT
Like most pathogenic bacteria, the Brucella spp. encounter extreme iron deprivation in their mammalian hosts. Two siderophores have been described for these bacteria, the simple catechol 2,3-dihydroxybenzoic acid (2,3-DHBA) and the more complex 2,3-DHBA-based siderophore brucebactin. Experimental evidence has clearly shown that 2,3-DHBA production is required for the wild type virulence of Brucella abortus 2308 in the reproductive tract of pregnant ruminants. In contrast, lack of catechol siderophore production does not compromise the capacity of this bacterium to establish and maintain chronic spleen infection in the mouse model. Surveys of the genome sequences of Brucella melitensis 16M and Brucella suis 1330 and experimental evidence obtained in the laboratory suggest that transport systems allowing the brucellae to utilise heme and ferric dicitrate as iron sources may be important for sustaining the intracellular lifestyle of the brucellae in host macrophages. The accumulation of excess intracellular iron can enhance oxidative damage to bacterial cells as a consequence of Fenton chemistry. Iron toxicity could be particularly problematic for the brucellae, as oxidative killing appears to be one of the primary mechanisms employed by host phagocytes to control the intracellular replication of these bacteria. Accordingly, experimental evidence and analysis of genome sequence data indicate that the Brucella spp. employ multiple transcriptional regulators including a ferric uptake regulator (Fur) to strictly control iron uptake in response to intracellular iron levels.
