Understanding the biomimetic properties of Gallium in Pseudomonas aeruginosa: a XAS and XPS study

Pyochelin (PCH) is a siderophore (extracellural chelator) produced by the pathogenic bacterium Pseudomonas aeruginosa (PAO). PCH is implicated in Iron (Fe3+) transport to PAO, and is crucial for its metabolism and pathogenicity. Due to chemical similarity with Fe3+, Gallium (Ga3+) interferes with vital Iron-dependent processes in bacterial cells, thereby opening new perspectives for the design of specific metal-based antibacterial drugs. However, a structural basis of the Fe3+-mimetic properties of Ga3+ complexed with the PCH siderophore is still lacking. A precise knowledge of the coordination chemistry at the metal site is one of the topmost issues in the production of novel biomimetic metal-based drugs. The elucidation of this issue by means of a deep structural spectroscopic investigation could lead to an improved interference with, or a specific inhibition of, relevant biological pathways. For this reason, we applied synchrotron radiation induced X-ray Photoelectron Spectroscopy (SR-XPS) and X-ray Absorption Spectroscopy (XAS) to probe the electronic nature and coordination chemistry of Fe3+ and Ga3+ coordinative sites in PCH metal complexes. Combined XAFS and SR-XPS studies allow to demonstrate that both Fe and Ga have the same valence state in Fe-PCH and Ga-PCH, and have the same octahedral coordination geometry. Moreover, the similar next neighbour distribution for Fe and Ga, resulting from the EXAFS data analysis, strongly supports the similar coordination chemistry at the origin of the biomimetic behaviour of Ga.