application): The applicants propose to exploit the metal-siderophore transport systems in bacteria to develop a new class of antibiotics. In particular, aerobactin and other siderophores have been shown to sequester essential metals, such as iron in bacteria. This process does not occur in mammalian cells. The applicants will evaluate the potential of these molecules and related analogues to transport toxic metals into the host bacteria. In addition, the applicants will utilize proprietary technology to prepare combinatorial libraries of aerobactin and related siderophores.
With the increasing frequency of bacterial strains that show resistance to all currently available antibiotics, there is a compelling need in the market for effective therapeutic options. This study will determine the feasibility of a new class of antibiotics which have a modality of action different from known drugs, and could result in a commercially successful drug.
