Numerous bacteria secrete low molecular weight compounds termed siderophores that have a high affinity for iron ions. Siderophores have a well-documented role as iron-scavenging chemicals, chelating iron ions in the environment whereupon the ferrisiderophores reenter the bacterial cells by means of specific cell-surface receptors. The iron is then released for incorporation into bacterial proteins. Here we show that in addition to its role as an iron-scavenger, the siderophore pyoverdine that is secreted by Pseudomonas aeruginosa regulates the production of at least three virulence factors (exotoxin A, an endoprotease, and pyoverdine itself), which are major contributors to the ability of this bacterium to cause disease. Regulation occurs through a transmembrane signaling system that includes an outer membrane receptor for ferripyoverdine, a signal-transducing protein that is predicted to extend from the periplasm into the cytoplasm, and a sigma factor. Expression of genes that form part of the regulon is triggered by pyoverdine so that this siderophore acts as a signaling molecule to control the production of secreted products. Recognition that a siderophore acts as a signaling molecule has important implications for the understanding of interactions between bacterial cells.
Death is likely to result in very extensive biochemical changes in all body tissues due to lack of circulating oxygen, altered enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites. These biochemical changes may provide chemical markers for helping to more accurately determine the time since death (post-mortem interval), which is challenging to establish with current observation-based methodologies. In this study blood pH and changes in concentration of six metabolites (lactic acid, hypoxanthine, uric acid, ammonia, NADH and formic acid) were examined post-mortem over a 96 hour period in blood taken from animal corpses (rat and pig) and blood from rats and humans stored in vitro. The pH and the concentration of all six metabolites changed post-mortem but the extent and rate of change varied. Blood pH in corpses fell from 7.4 to 5.1. Concentrations of hypoxanthine, ammonia, NADH and formic acid all increased with time and these metabolites may be potential markers for post-mortem interval. The concentration of lactate increased and then remained at an elevated level and changes in the concentration were different in the rat compared to the human and pig. This is the first systematic study of multiple metabolic changes post-mortem and demonstrates the nature and extent of the changes that occur, in addition to identifying potential markers for estimating post-mortem interval.