Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection

Mol Microbiol. 2009 May;72(3):763-78. doi: 10.1111/j.1365-2958.2009.06684.x.


Bacillus anthracis proliferates to high levels within vertebrate tissues during the pathogenesis of anthrax. This growth is facilitated by the acquisition of nutrient iron from host haem. However, haem acquisition can lead to the accumulation of toxic amounts of haem within B. anthracis. Here, we show that B. anthracis resists haem toxicity by sensing haem through the HssRS two-component system, which regulates expression of the haem-detoxifying transporter HrtAB. In addition, we demonstrate that B. anthracis exhibits elevated HssRS function compared with its evolutionary relative Staphylococcus aureus. Elevated haem sensing is likely required by B. anthracis due to the significant haem sensitivity exhibited by members of the genus Bacilli. We also demonstrate that B. anthracis depends on conserved residues within the previously uncharacterized sensing domain of the histidine kinase HssS for HssS function. Finally, we show that the haem- and HssRS-regulated hrtAB promoter is activated in a murine model of anthrax. These results demonstrate the evolutionary conservation of haem sensing among multiple Gram-positive bacteria and begin to provide a mechanistic explanation for the haem resistance of B. anthracis. Further, these data suggest that haem stress is experienced by bacterial pathogens during infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacillus anthracis / enzymology*
  • Bacillus anthracis / genetics
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Genetic Complementation Test
  • Hemin / metabolism*
  • Histidine Kinase
  • Mice
  • Mice, Inbred A
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics


  • Bacterial Proteins
  • Hemin
  • Protein Kinases
  • Histidine Kinase
  • Serine Endopeptidases
  • htrA protein, Bacillus anthracis