Dual Effect of Synthetic Aminoglycosides: Antibacterial Activity against Bacillus anthracis and Inhibition of Anthrax Lethal Factor

摘要

Anthrax is an infectious disease caused by toxigenic strains of the Gram-positive Bacillus anthracis.[1] If inhaled, B. anthracis spores rapidly reach the regional lymphonodes of the lungs, where they germinate and release anthrax toxins.[2] These toxins inhibit the adaptive immune response, thereby enabling the bacteria to reach the blood system, where they cause bacteremia and toxemia, which rapidly kill the host. Nontoxigenic strains of B. anthracis are poorly pathogenic, thus indicating that the anthrax toxins play a major role from the very beginning of infection to death. Since anthrax is asymptomatic until the bacterium reaches the blood,[1], [2] the development of antitoxin therapeutic compounds for preventive use or for use in combination with antibiotics is of high urgency.[3] Alternatively, it would be highly beneficial if the developed material were bifunctional, with the ability to inactivate the released toxins and, in parallel, to function as an antibiotic.