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Research

Dr. Cendrowski studies host-pathogen interactions of the Gram-positive spore-forming bacteria, Bacillus anthracis , which is the causative agent of anthrax . Dr. Cendrowski is specifically interested in characterization of the B. anthracis iron regulon and the host-derived iron signals that influence this regulon during an anthrax infection.

The systemic form of a B. anthracis infection, which can arise from inhalation, ingestion, or (less commonly) cutaneous inoculation of infectious B. anthracis endospores can be characterized as proceeding in stages: 1. an early intracellular establishment stage within macrophages, 2. extracellular stages that begin in lymph nodes, and 3. a rapid spread from the lymphatics into the bloodstream, which results in massive bacteremia, sepsis and death within a few days of onset. Since most bacteria require iron to survive and replicate within the host, pathogens have evolved or adapted siderophore-dependent mechanisms of high affinity iron acquisition. Some bacterial pathogens produce siderophores, which are small (molecular weight) non-protein molecules capable of stripping iron from otherwise inaccessible iron sources (e.g., transferrin) in response to the innately iron-impoverished niches in which it grows within the host.

To this end, B. anthracis synthesizes a catechol-type siderophore termed petrobactin that is critical for iron acquisition during infection. In my lab, we model anthrax using non-lethal B. anthracis strains; through the application of bacterial genetics (forward and reverse), as well as molecular, and biochemical techniques we have begun to characterize additional factors that are required for the synthesis and transport of petrobactin. Related to this, in vitro studies have suggested that a complex regulatory mechanism may be involved in petrobactin synthetase expression and that the expression of multiple (possibly redundant) transporter proteins is linked to the production of petrobactin. Additionally, the identification of host-related factors that influence or are influenced by B. anthracis petrobactin are of interest and methods to probe this area are currently being developed.