Gram-Negative Bacterial Wound Infections.

摘要

Biochemical and functional analyses of the A. baumannii AB5075 wild type parental strain and isogenic insertion derivatives showed that inactivation of genes coding for biosynthesis and transport of the high- affinity siderophore acinetobactin drastically affects the capacity of this strain to grow under iron-limiting laboratory conditions as well as to infect and kill G. mellonella larvae and BALB/c mice in experimental infection assays. These results validate AB5075 as a proper model strain to study virulence under in vitro and in vivo conditions and demonstrate the central role the acinetobactin-mediated iron acquisition system plays in its virulence. Equally relevant is the finding that all A. baumannii wound isolates tested were sensitive to Ga-PPIX independent of the composition of the media. These observations support our goal of using this non-ferric metalloporphyrin derivative as an anti-microbial agent in a wound infection model. Such an approach is feasible because Ga-PPIX does not display detectable cell and animal toxicity within the concentration range we plan to test based on data obtained with other pathogens. Although these observations are encouraging regarding the potential use of Ga-PPIX as an alternative to treat infections caused by MDR A. baumannii strains, the efficacy of this non-ferric metalloporphyrin derivative against other wound pathogens is not conclusive and requires some additional studies. Similar conclusions were obtained using gallium nitrate, the activity of which depends on the composition of the media. The successful implementation of a tissue culture model, which examines critical host-pathogen interactions, has the potential for providing novel and critical information on the pathobiology of bacteria that cause severe human infections.