A Mechanistically Novel Antibiotic for Anthrax

DESCRIPTION (provided by applicant): Anthrax is an infectious illness that has been known for many years, largely in rural settings, but since the terrorist attacks of 9-11, has recently emerged as a major national security concern. Bacillus anthracis, the causative agent of anthrax, exists naturally in various forms and is now considered a bioterrorism agent. There is fear that this microbe could develop or be developed into forms that are highly resistant to current antibiotics (such as ciprofloxacin, penicillin and doxycycline), thus rendering our public health system's ability to control anthrax infections ineffective. The mission to identify new drugs that can be used to treat anthrax infections, and which operate through a unique mechanism of action, is a daunting task. Consequently, there is presently a high commercial potential for effective antibiotics that can be stockpiled for on-demand distribution by the federal agencies dudng the event of a terrorist attack. Our approach toward addressing this problem is to demonstrate the potent antibacterial capabilities of a new class of synthetic antibiotics, recently developed in our laboratory, against the microbe B. anthracis. These antibiotic compounds have been patented by University of South Flodda. Although we are investigating these compounds for their anti-MRSA (Methicillin Resistant Staphylococcus aureus) and anticancer properties, we are also focused on their bacteriostatic effects on Bacillus anthracis. Our goal is to develop these compounds into a new class of anti-anthrax antibiotics that will be highly effective in the event of a large scale anthrax attack. Our proposal posts two Specific Aims: (1) to confirm the biochemical basis for the antibacterial activity of these substances towards B. anthracis, through radiolabeling experiments, and (2) to find suitable drug candidates whose activity is as good as or better than the current anti-anthrax drugs through synthesis and evaluation of compound libraries. The conclusion we hope to draw is that these compounds are highly effective against avirulent and virulent strains of B. anthracis and operate though a unique mechanism of action. The most premising drug candidates from this Phase I feasibility study will be taken forward into Phase II to conduct animal testing and pharmacokinetics studies. Thus, finding suitable compounds that could be brought into Phase II is critical.