Chelating Mechanisms of Transition Metals by Bacterial Metallophores “Pseudopaline and Staphylopine”: A Quantum Chemical Assessment

Abstract

In bacterial pathology, metallophores fabricated by bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa are exported to surrounding physiological media via a specific process to sequester and import metals, resulting in enhanced virulence of the bacteria. While these mechanisms are understood at qualitative levels, our investigation presents a complementary original view based on quantum chemical computations. Further understanding of the active centers in particular was provided for pseudopaline and staphylopine metallophores, which were described chemically and with vibration spectroscopy. Then, for complexes formed with a range of transition metal divalent ions (Ni, Cu, and Zn), description and analyses of the frontier molecular orbitals (FMOs) are provided, highlighting a mechanism of metal-to-ligand charge transfer (MLCT), based on excited-states calculations (time-dependent density functional theory (TD-DFT)) at the basis of the delivery of the metallic ionic species to the bacterial medium, leading eventually to its enhanced virulence. Such investigation gains importance especially in view of stepwise syntheses of metallophores in the laboratory, providing significant progress in the understanding of mechanisms underlying the enhancement of bacterial pathologies.

Interchangeable utilization of metals: New perspectives on the impacts of metal ions employed in ancient and extant biomolecules

“…Metallophores belong to a family of small molecules that bind various metal ions in the extracellular environment, following by active import of chelated metal complexes inside the bacterial cells. Normally, metallophores are divided into different groups based on their affinity toward a specific metal, such as siderophores for Fe, chalcophore for Cu, manganesophore for Mn, nickelophore for Ni, and zincophore for Zn (( 218 ), references therein). Staphylopine produced by the pathogenic bacteria S. aureus stands out as a broad-spectrum affinity metallophore, as it is able of chelating various transition metals ( 219 ), thus efficiently overpowering host immunity.…”

“…By forming a complex with metal ion through ionic and coordination bonding (detailed in Ref. ( 218 )), metal chelators alter metals' chemical properties, making metal ions unavailable for biological activities within metabolic pathways. As such, deferiprone, deferoxamine, and deferasirox are used for the removal of Fe during treatment of thalassemia, myelodysplasia, and sickle cell anemia, and penicillamine is used to deplete excessive Cu during Wilson's disease therapy ( 252 ).…”

The Key Element Role of Metallophores in the Pathogenicity and Virulence of Staphylococcus aureus: A Review

“…This last contains imidazole ring and three carboxylic groups. It is an opine metallophore and can chelate several metal ions (nickel, zinc, cobalt, iron and copper), so it is considered a broad-spectrum metallophore [ 80 ]. The import of these wide range of metal ions via staphylopine depends on the metal nature and concentration along with the S. aureus growth status [ 79 ].…”

Nickel stress-tolerance in plant-bacterial associations

“…However, their structural nature is variable and they bind different metals and even metalloids (Retamal-Morales et al, 2018). Such complexes are transported into the periplasm by TonB-dependent transporters (TBDT), and are transported across the plasma membrane by ATP-binding cassette (ABC) transporters in both Gram-negative and Gram-positive bacteria (Ghssein & Matar, 2018). Other metallophores are found and described also for their ability to uptake metals other than iron, such as, for example, nickelophore for nickel (Lebrette et al, 2015), and zincophore for zinc (Bobrov et al, 2017).…”