Pseudomonas aeruginosa is a dangerous opportunistic bacterium responsible for frequently lethal hospital (nosocomial) infections. It endangers especially severely injured patients suffering from large wounds or severe burns, as well as persons whose immune system is weakened. An extremely critical situation exists for patients suffering from mucoviscidosis (cystic fibrosis), when P. aeruginosa infects the bronchial tubes. P. aeruginosa is resistant against many desinfecting agents and, more important, an increasing number of strains especially from hospital isolates have become highly resistant against most antibiotics. The low permeability of the outer membrane and an active export mechanism for low molecular weight substances are the main reasons for the resistance. In addition, b-lactamase activity affects treatment with b-lactam antibiotics. An approach to overcome the problem of resistance lies in the synthesis of antibiotics conjugated with compounds active as siderophores. In this way the transport ways for iron complexes into the cell can be used (Trojan Horse strategy), and the presence of large substituents reduces the export and the b-lactamase activity. The results obtained with natural (pyoverdins) and synthetic (mainly catecholate) siderophores will be reviewed.
Keywords: Siderophore Antibiotic Conjugates, Trojan Horses, Pseudomonas aeruginosa, lactamase, iron regulated outer membrane proteins, PYOVERDIN LACTAM CONJUGATES, SIDEROPHORE-b-LACTAM, Catecholates, Hydroxamates
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