Gram-Negative Bacterial Wound Infections.

摘要

Bacterial strains from wounded soldiers are iron acquisition and biofilm formation proficient. In the case of the A. baumannii AB5075 model strain, the expression of a fully functional acinetobactin-mediated iron acquisition system is critical when tested under laboratory conditions or using ex vivo and in vivo experimental infection models. Accordingly, the presence of Ga-PPIX significantly reduced the growth of all tested A. baumannii strains independently of their site of isolation or resistance phenotypes. However, the activity of Ga-PPIX against bacteria different from A. baumannii was variable as it was the activity of Ga nitrate, which also depended on the free-iron content of the media. Thus, these observations support the idea of using iron acquisition activity/functions as targets to treat infections with the biologically inactive Ga-PPIX metalloporphyrin derivative, which negatively impacts bacterial functions involved in critical host-pathogen interactions. These observations also support the potential value of proposed animal experiments that will not only confirm the role of iron acquisition in the virulence of A. baumannii, but also test the antimicrobial activity of Ga-PPIX in experimental wound infections. Preliminary studies showed that the value of iron acquisition as a target could be enhanced by the observation that iron-regulated A. baumannii hemolysins/cytolysins, which could provide intracellular iron by cell/tissue destruction, could be targeted using a phosphatidylcholine analog as it was done with other relevant human pathogens. In contrast, tested antibiofilm agents not only produced a modest negative effect on their biogenesis, but also increased their formation or enhanced the cell damage caused by the AB5075 wound isolate. The genetic and molecular bases of these unexpected observations could be elucidated by comparative genomics studies once the genomes all isolates are fully sequenced and annotated.