Understanding the biomimetic properties of gallium in Pseudomonas aeruginosa: an XAS and XPS study

• Published in: Dalton transactions : an international journal of inorganic chemistry 2017-05, Vol.46 (21), p.7082-7091
• Main Authors: Porcaro, F, Bonchi, C, Ugolini, A, Frangipani, E, Polzonetti, G, Visca, P, Meneghini, C, Battocchio, C
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacteria; Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Biomimetics; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - metabolism; Drugs; Gallium; Gallium - chemistry; Iron; Iron - chemistry; Iron - metabolism; Molecular Conformation; Phenols - chemistry; Photoelectron Spectroscopy; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - metabolism; Strontium; Thiazoles - chemistry; X rays; X-Ray Absorption Spectroscopy
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c7dt00651a

Pyochelin (PCH) is a siderophore (extracellular chelator) produced by the pathogenic bacterium Pseudomonas aeruginosa (PAO). PCH is implicated in iron (Fe ) transport to PAO, and is crucial for its metabolism and pathogenicity. Due to the chemical similarity with Fe , gallium (Ga ) interferes with vital iron-dependent processes in bacterial cells, thereby opening new perspectives for the design of specific metal-based antibacterial drugs. However, the structural basis for the Fe -mimetic properties of Ga 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. 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 Fe and Ga coordinative sites in PCH metal complexes. Combined XAFS and SR-XPS studies allow us 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, a similar next neighbour distribution for Fe and Ga, resulting from the EXAFS data analysis, strongly supports similar coordination chemistry at the origin of the biomimetic behaviour of Ga.