Biomaterial Database

Structure-function studies of acinetobactin analogs. 2017

Justin A Shapiro, and Timothy A Wencewicz

Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, USA. wencewicz@wustl.edu.

Pathogenic Acinetobacter baumannii excrete the siderophore pre-acinetobactin as an iron-scavenging virulence factor. Pre-acinetobactin is a 2,3-dihydroxy-phenyl oxazoline that undergoes pH-dependent isomerization to the isooxazolidinone form acinetobactin in order to expand the pH range for iron acquisition by A. baumannii. In this study we establish important structure-function relationships for the kinetics of isomerization, iron(iii) binding, and siderophore utilization by A. baumannii. We showed that electronic properties of the phenyl oxazoline influence isomerization kinetics and iron(iii) binding. We found that iron(iii) chelation was directly correlated with A. baumannii utilization. Our studies provide important structural and mechanistic insight for understanding how pathogenic A. baumannii uses pre-acinetobactin as a 2-for-1 iron-scavenging siderophore virulence factor.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007501	Iron	A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.	Iron-56,Iron 56
D007536	Isomerism	The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Isomerisms
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010080	Oxazoles	Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.	Oxazole,1,3-Oxazolium-5-Oxides,Munchnones,1,3 Oxazolium 5 Oxides
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000151	Acinetobacter Infections	Infections with bacteria of the genus ACINETOBACTER.	Mimae Infections,Infections, Acinetobacter,Infections, Mimae,Acinetobacter Infection,Infection, Acinetobacter,Infection, Mimae,Mimae Infection
D017262	Siderophores	Low-molecular-weight compounds produced by microorganisms that aid in the transport and sequestration of ferric iron. (The Encyclopedia of Molecular Biology, 1994)	Siderophore,Siderochromes
D037521	Virulence Factors	Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)	Pathogenicity Factor,Pathogenicity Factors,Virulence Factor,Factor, Pathogenicity,Factor, Virulence,Factors, Pathogenicity,Factors, Virulence
D040981	Acinetobacter baumannii	A species of gram-negative, aerobic bacteria, commonly found in the clinical laboratory, and frequently resistant to common antibiotics.	Bacterium anitratum