Grant: Project Grant

Acinetobacter baumannii is an emerging opportunistic pathogen that causes an array of infections, including serious and often fatal illnesses such pneumonia and sepsis. The rapid rise of multi- and even pandrug resistance in A. baumannii led the WHO to designate A. baumannii as a priority "critical" pathogen for therapeutic development. The rational design of new treatments strategies, however, urgently necessitates a much-improved knowledge of the physiology of A. baumannii during infection. Histamine, as a major immunomodulator within the host, promotes vasodilation and vascular permeability, the latter of which allows immune cells to enter damaged tissues to counter infection. Interestingly, A. baumannii can convert histidine into histamine and incorporate histamine into a key iron-binding molecule that is important for infection. Additionally, we have strong preliminary data to support that histamine that is encountered in the environment can be brought into the A. baumannii cell and promote iron-restricted growth. Our goals in this research are to elucidate the implications of histamine on A. baumanii physiology, especially during infection. Intriguingly, antihistamines have recently been shown to have antibacterial properties and so our work will also characterize the role that preexisting antihistamine-based therapeutics play in inhibiting A. baumannii growth and infection. The purpose of this research project is to interrogate the basic physiology of A. baumannii, especially during infection, with a focus on the impact of histamine on disease outcomes.