Brucella abortus siderophore 2,3-dihydroxybenzoic acid (DHBA) facilitates intracellular survival of the bacteria

Abstract

Siderophores are low molecular weight molecules that allow bacteria to acquire iron from host cell proteins. 2,3-dihydroxybenzoic acid (DHBA) is the only known siderophore produced by the intracellular pathogen Brucella abortus. Here its role in virulence was assessed by evaluating the ability of a mutant with a disruption of the entC gene to survive and replicate in vitro in murine and bovine cells and in vivo in resistant and susceptible murine hosts. It was hypothesized that DHBA is vital for bacterial virulence by its ability to chelate intracellular iron thereby preventing generation of anti-bacterial hydroxyl radicals via the Haber-Weiss reaction, to scavenge reactive oxygen intermediates and for acquisition of iron needed for nutritional purposes. The data showed DHBA played a significant role for bacterial survival in host cells after infection including in murine macrophages cultured in the presence and absence of exogenous interferon-gamma (IFN-gamma) and in bovine trophoblasts supplemented with erythritol. In severely iron-depleted conditions, DHBA was also found to be essential for growth in murine macrophages. Despite these deficiencies, the absence of DHBA had no long-term significant effect on the number of CFU recovered in vivo from either the Brucella-resistant C57BL/6 mice or Brucella-susceptible IFN-gamma knock-out C57BL/6 mice.