Pseudomonas aeruginosa is an important opportunistic pathogen responsible for high mortality in cystic fibrosis and hospital-acquired infections. The damage caused by Pseudomonas aeruginosa is highly dependent upon the ability of the organism to obtain iron from the host. If iron is not available to the organism, the bacterium is unable to grow or cause disease. I am concentrating on the study of how this bacterium acquires iron from the host. P. aeruginosa produces iron-sequestering compounds called siderophores which help the bacterium get iron from the host or environment. One of these siderophores is called pyochelin and is the subject of my work. The bacterium is able to transport iron into the cell when it is bound to pyochelin. This occurs through a surface protein receptor on the bacterium. The gene for this surface protein has been cloned and sequenced. The receptor for the iron-pyochelin complex is quite similar to receptors for other iron-siderophore complexes which have little structural similarities to the iron-pyochelin complex. This result indicates that many bacteria use very similar systems for the transport of iron into the cell. The similarities of these systems suggest that antimicrobial chemotherapy based on iron-siderophore transport systems may be applicable to a broad range of bacterial infections. An additional finding is that the iron-pyochelin receptor is expressed only under conditions of low iron available. This iron- regulated production of the receptor is caused by a specific DNA sequence called the 'iron box', and this is the first example of such a DNA sequence to be identified in P. aeruginosa.
