This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bacteria that cause diseases have a variety of creative methods which they use to invade a host and propagate. One of the more successful in their arsenal is toxins which the bacteria secrete into the milieu to kill host cells in the immediate environment, thereby permitting deeper penetration into tissues, or perhaps to incapacitate host defense responses. For these toxin-producing bacteria, antibiotic treatment alone is insufficient because the damage done by the toxins is often directly linked to lethality. Traditional methods to screen for anti-toxin drugs are usually survival studies in rodent models which are laborious and provide only limited information. The current study develops a new approach using targeted magnetic resonance imaging techniques to directly visualize where a toxin localizes in vivo and subsequent effects of potential anti-toxin therapeutics. Preliminary data obtained with a toxin component from Bacillus anthracis (anthrax) demonstrate renal and liver localization in toxin-sensitive mice under inflammatory conditions. Data acquisition is rapid with concomitant physiological monitoring. Continued development of appropriate imaging probes will improve sensitivity and selectivity. The methodology should be applicable to a variety of toxins and will contribute to more rapid development, screening, and pre-clinical testing of anti-toxin drugs.
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