Synthetic Mimics of Native Siderophores Disrupt Iron Trafficking in .

Many pathogenic bacteria biosynthesize and excrete small molecule metallophores, known as siderophores, that are used to extract ferric iron from host sources to satisfy nutritional need. Native siderophores are often structurally complex multidentate chelators that selectively form high-affinity octahedral ferric iron complexes with defined chirality recognizable by cognate protein receptors displayed on the bacterial cell surface. Simplified achiral analogues can serve as synthetically tractable siderophore mimics with potential utility as chemical probes and therapeutic agents to better understand and treat bacterial infections, respectively.

Fimsbactin and Acinetobactin Compete for the Periplasmic Siderophore Binding Protein BauB in Pathogenic Acinetobacter baumannii.

Environmental and pathogenic microbes produce siderophores as small iron-binding molecules to scavenge iron from natural environments. It is common for microbes to produce multiple siderophores to gain a competitive edge in mixed microbial environments. Strains of human pathogenic Acinetobacter baumannii produce up to three siderophores: acinetobactin, baumannoferrin, and fimsbactin.

Crystal Structure of the Siderophore Binding Protein BauB Bound to an Unusual 2:1 Complex Between Acinetobactin and Ferric Iron.

The critical role that iron plays in many biochemical processes has led to an elaborate battle between bacterial pathogens and their hosts to acquire and withhold this critical nutrient. Exploitation of iron nutritional immunity is being increasingly appreciated as a potential antivirulence therapeutic strategy, especially against problematic multidrug resistant Gram-negative pathogens such as Acinetobacter baumannii. To facilitate iron uptake and promote growth, A.

Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria.

Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore.

Metal selectivity by the virulence-associated yersiniabactin metallophore system.

Uropathogenic Escherichia coli secrete siderophores during human infections. Although siderophores are classically defined by their ability to bind iron(III) ions, the virulence-associated siderophore yersiniabactin was recently found to bind divalent copper ions during urinary tract infections. Here we use a mass spectrometric approach to determine the extent of non-iron(III) metal interactions by yersiniabactin and its TonB-dependent outer membrane importer FyuA.

Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic.

Many Gram-negative bacteria interact with extracellular metal ions by expressing one or more siderophore types. Among these, the virulence-associated siderophore yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu(II)-Ybt) complexes that are detectable in infected patients. Here we show that Ybt-expressing E.

Radical Cation/Radical Reactions: A Fourier Transform Ion Cyclotron Resonance Study of Allyl Radical Reacting with Aromatic Radical Cations.

A method for the study of reactions of open-shell neutrals (radicals) and radical cations is described. Pyrolysis (25-1500 degrees C) of thermally labile compounds, such as, 1,5-hexadiene via a Chen nozzle yields a seeded beam of reactive species in helium. The pyrolysis products are then analyzed by electron ionization (EI) or reacted with stored ions.

Probing Ca2+-induced conformational changes in porcine calmodulin by H/D exchange and ESI-MS: effect of cations and ionic strength.

We applied a new method, "protein-ligand interaction using mass spectrometry, titration, and H/D exchange" (PLIMSTEX) [Zhu, M. M. (2003) J.