Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence

Area of Science:

• Microbiology
• Pathogen Biology
• Bacterial Pathogenesis

Background:

• Systemic anthrax progresses through intracellular and extracellular stages.
• Bacteria, including Bacillus anthracis, require iron for growth.
• Host iron limitation necessitates high-affinity bacterial iron acquisition mechanisms.

Purpose of the Study:

• To investigate the role of two putative siderophore synthesis operons, anthrabactin (bac) and anthrachelin (asb), in Bacillus anthracis iron acquisition.
• To determine the necessity of these pathways for bacterial growth, intracellular survival, and virulence.

Main Methods:

• Generated gene deletion mutants in B. anthracis Sterne 34F2 for the anthrabactin (bacCEBF) and anthrachelin (asbA) pathways.
• Assessed siderophore production under iron-depleted conditions.
• Evaluated bacterial growth in macrophages (MPhi) and virulence in a murine model.

Main Results:

• Both DeltaasbA and DeltabacCEBF mutants showed reduced siderophore production in iron-depleted media.
• Only the DeltaasbA mutant exhibited attenuated growth under iron-depleted conditions.
• The DeltaasbA mutant was severely attenuated for growth in macrophages and for virulence in mice.
• The DeltabacCEBF mutant showed no significant phenotypic differences compared to the parental strain.

Conclusions:

• Anthrachelin, synthesized via the asbA gene, is essential for Bacillus anthracis iron assimilation during the intracellular stage.
• Anthrabactin is not required for iron uptake or virulence in the studied B. anthracis model.
• Targeting the anthrachelin pathway could be a strategy to combat anthrax infections.