关键词：细菌性疾病,革兰氏阴性细菌;传染病;细菌;化学衍生品;临床医学;协作技术;补充(生物学);基因工程
摘 要：Work done during the first year of the award resulted in the identification and characterization of a set of 29 A. baumannii strains isolated from wounded military personnel with regard to their capacity to grow under iron-limiting conditions, produce iron chelators siderophores and form biofilms on abiotic surfaces found in medical settings. This analysis indicates that all isolates form biofilms on abiotic surfaces and different strains produce and/or use different siderophores when cultured under iron chelation. However, all tested strains produce dihydroxybenzoic acid derivatives, the synthesis of which could be used as a therapeutic target. Accordingly, salicylic acid derivatives seem to inhibit bacterial growth under iron chelation. Equally encouraging is the observation that gallium-containing derivatives, particularly Gaprotoporphyrin IX, inhibit bacterial growth independently of the iron and nutrient content of the medium. These are encouraging observations that will be tested in animal models proposed in this project and promote future basic studies since the mechanisms by which Ga-PPIX inhibit A. baumannii growth are unknown. Work done during this first year together with preliminary data collected by collaborators also resulted in the selection of the AB5075 isolate as a model strain for more extensive studies. This clinical isolate proved to be virulent when tested using ex vivo and in vivo experimental infection models and amenable to genetic manipulations, including high throughput insertion mutagenesis and genetic complementation with shuttle cloning vectors under construction.