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Results: 1 to 8 of 8

Publication Record


exhibits heterogeneous siderophore production within the vertebrate host.
Perry WJ, Spraggins JM, Sheldon JR, Grunenwald CM, Heinrichs DE, Cassat JE, Skaar EP, Caprioli RM
(2019) Proc Natl Acad Sci U S A 116: 21980-21982
MeSH Terms: Abscess, Animals, Citrates, Host-Pathogen Interactions, Iron, Mice, Ornithine, Siderophores, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Staphylococcal Infections, Staphylococcus aureus
Show Abstract · Added January 22, 2020
Siderophores, iron-scavenging small molecules, are fundamental to bacterial nutrient metal acquisition and enable pathogens to overcome challenges imposed by nutritional immunity. Multimodal imaging mass spectrometry allows visualization of host-pathogen iron competition, by mapping siderophores within infected tissue. We have observed heterogeneous distributions of siderophores across infectious foci, challenging the paradigm that the vertebrate host is a uniformly iron-depleted environment to invading microbes.
Copyright © 2019 the Author(s). Published by PNAS.
0 Communities
3 Members
0 Resources
11 MeSH Terms
Synthesis of the Siderophore Coelichelin and Its Utility as a Probe in the Study of Bacterial Metal Sensing and Response.
Williams JC, Sheldon JR, Imlay HD, Dutter BF, Draelos MM, Skaar EP, Sulikowski GA
(2019) Org Lett 21: 679-682
MeSH Terms: Iron, Molecular Probes, Oligopeptides, Pseudomonas aeruginosa, Siderophores
Show Abstract · Added April 7, 2019
A convergent total synthesis of the siderophore coelichelin is described. The synthetic route also provided access to acetyl coelichelin and other congeners of the parent siderophore. The synthetic products were evaluated for their ability to bind ferric iron and promote growth of a siderophore-deficient strain of the Gram-negative bacterium Pseudomonas aeruginosa under iron restriction conditions. The results of these studies indicate coelichelin and several derivatives serve as ferric iron delivery vehicles for P. aeruginosa.
0 Communities
1 Members
0 Resources
MeSH Terms
Transition Metals and Virulence in Bacteria.
Palmer LD, Skaar EP
(2016) Annu Rev Genet 50: 67-91
MeSH Terms: Animals, Bacteria, Bacterial Infections, Deficiency Diseases, Diet, Heme, Host-Pathogen Interactions, Humans, Iron, Iron Overload, Metals, Siderophores
Show Abstract · Added April 8, 2017
Transition metals are required trace elements for all forms of life. Due to their unique inorganic and redox properties, transition metals serve as cofactors for enzymes and other proteins. In bacterial pathogenesis, the vertebrate host represents a rich source of nutrient metals, and bacteria have evolved diverse metal acquisition strategies. Host metal homeostasis changes dramatically in response to bacterial infections, including production of metal sequestering proteins and the bombardment of bacteria with toxic levels of metals. In response, bacteria have evolved systems to subvert metal sequestration and toxicity. The coevolution of hosts and their bacterial pathogens in the battle for metals has uncovered emerging paradigms in social microbiology, rapid evolution, host specificity, and metal homeostasis across domains. This review focuses on recent advances and open questions in our understanding of the complex role of transition metals at the host-pathogen interface.
0 Communities
2 Members
0 Resources
12 MeSH Terms
Structural analysis of cytochrome P450 105N1 involved in the biosynthesis of the zincophore, coelibactin.
Zhao B, Moody SC, Hider RC, Lei L, Kelly SL, Waterman MR, Lamb DC
(2012) Int J Mol Sci 13: 8500-13
MeSH Terms: Bacterial Proteins, Catalytic Domain, Crystallography, X-Ray, Cytochrome P-450 Enzyme System, Models, Molecular, Oxazoles, Protein Structure, Secondary, Siderophores, Streptomyces coelicolor, Thiazoles, Zinc
Show Abstract · Added February 12, 2015
Coelibactin is a putative non-ribosomally synthesized peptide with predicted zincophore activity and which has been implicated in antibiotic regulation in Streptomyces coelicolor A3(2). The coelibactin biosynthetic pathway contains a stereo- and regio-specific monooxygenation step catalyzed by a cytochrome P450 enzyme (CYP105N1). We have determined the X-ray crystal structure of CYP105N1 at 2.9 Å and analyzed it in the context of the bacterial CYP105 family as a whole. The crystal structure reveals a channel between the α-helical domain and the β-sheet domain exposing the heme pocket and the long helix I to the solvent. This wide-open conformation of CYP105N1 may be related to the bulky substrate coelibactin. The ligand-free CYP105N1 structure has enough room in the substrate access channel to allow the coelibactin to enter into the active site. Analysis of typical siderophore ligands suggests that CYP105N1 may produce derivatives of coelibactin, which would then be able to chelate the zinc divalent cation.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Thematic minireview series: Metals in Biology 2012.
Guengerich FP
(2012) J Biol Chem 287: 13508-9
MeSH Terms: Animals, Catalytic Domain, Copper, Homeostasis, Humans, Hydrogenase, Iron, Lipocalins, Macrophages, Manganese, Metals, Models, Biological, Siderophores
Show Abstract · Added May 26, 2014
Metals are present in about one-half of the protein structures available and also have critical roles in nucleic acid biochemistry. This prologue introduces the fourth of the Thematic Minireview Series on Metals in Biology, which deals with several topics involving iron, manganese, copper, and other metals. The six minireviews discuss metal transport and intracellular homeostasis, including chaperones and siderophores, maturation of the diiron active sites in hydrogenases, the balance between manganese and iron, and copper homeostasis relevant to pathogens.
0 Communities
1 Members
0 Resources
13 MeSH Terms
A battle for iron: host sequestration and Staphylococcus aureus acquisition.
Haley KP, Skaar EP
(2012) Microbes Infect 14: 217-27
MeSH Terms: Animals, Bacterial Proteins, Gene Expression Regulation, Bacterial, Heme, Heme Oxygenase (Decyclizing), Hemoglobins, Host-Pathogen Interactions, Humans, Iron, Siderophores, Staphylococcal Infections, Staphylococcus aureus, Virulence Factors
Show Abstract · Added February 11, 2016
The use of iron as an enzymatic cofactor is pervasive in biological systems. Consequently most living organisms, including pathogenic bacteria, require iron to survive and replicate. To combat infection vertebrates have evolved sophisticated iron sequestration systems against which, pathogenic bacteria have concomitantly evolved equally elaborate iron acquisition mechanisms.
Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Molecular mechanisms of Staphylococcus aureus iron acquisition.
Hammer ND, Skaar EP
(2011) Annu Rev Microbiol 65: 129-47
MeSH Terms: Animals, Bacterial Proteins, Gene Expression Regulation, Bacterial, Humans, Iron, Siderophores, Staphylococcal Infections, Staphylococcus aureus
Show Abstract · Added February 11, 2016
The unique redox potential of iron makes it an ideal cofactor in diverse biochemical reactions. Iron is therefore vital for the growth and proliferation of nearly all organisms, including pathogenic bacteria. Vertebrates sequester excess iron within proteins in order to alleviate toxicity and restrict the amount of free iron available for invading pathogens. Restricting the growth of infectious microorganisms by sequestering essential nutrients is referred to as nutritional immunity. In order to circumvent nutritional immunity, bacterial pathogens have evolved elegant systems that allow for the acquisition of iron during infection. The gram-positive extracellular pathogen Staphylococcus aureus is a commensal organism that can cause severe disease when it gains access to underlying tissues. Iron acquisition is required for S. aureus colonization and subsequent pathogenesis. Herein we review the strategies S. aureus employs to obtain iron through the production of siderophores and the consumption of host heme.
0 Communities
1 Members
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8 MeSH Terms
Iron acquisition functions expressed by the human pathogen Acinetobacter baumannii.
Zimbler DL, Penwell WF, Gaddy JA, Menke SM, Tomaras AP, Connerly PL, Actis LA
(2009) Biometals 22: 23-32
MeSH Terms: Acinetobacter baumannii, Gallium, Gene Expression Regulation, Bacterial, Hemin, Hemoglobins, Humans, Iron, Multigene Family, Siderophores
Show Abstract · Added January 13, 2014
Acinetobacter baumannii is a gram-negative bacterium that causes serious infections in compromised patients. More recently, it has emerged as the causative agent of severe infections in military personnel wounded in Iraq and Afghanistan. This pathogen grows under a wide range of conditions including iron-limiting conditions imposed by natural and synthetic iron chelators. Initial studies using the type strain 19606 showed that the iron proficiency of this pathogen depends on the expression of the acinetobactin-mediated iron acquisition system. More recently, we have observed that hemin but not human hemoglobin serves as an iron source when 19606 isogenic derivatives affected in acinetobactin transport and biosynthesis were cultured under iron-limiting conditions. This finding is in agreement with the observation that the genome of the strain 17978 has a gene cluster coding for putative hemin-acquisition functions, which include genes coding for putative hemin utilization functions and a TonBExbBD energy transducing system. This system restored enterobactin biosynthesis in an E. coli ExbBD deficient strain but not when introduced into a TonB mutant. PCR and Southern blot analyses showed that this hemin-utilization gene cluster is also present in the 19606 strain. Analysis of the 17978 genome also showed that this strain harbors genes required for acinetobactin synthesis and transport as well as a gene cluster that could code for additional iron acquisition functions. This hypothesis is in agreement with the fact that the inactivation of the basD acinetobactin biosynthetic gene did not affect the growth of A. baumannii 17978 cells under iron-chelated conditions. Interestingly, this second iron uptake gene cluster is flanked by perfect inverted repeats and includes transposase genes that are expressed transcriptionally. Also interesting is the observation that this additional cluster could not be detected in the type strain 19606, an observation that suggests some significant differences in the iron uptake capacity between these two A. baumannii strains. Transposome mutagenesis of the strain 19606 resulted in the isolation of a derivative unable to grow under iron-chelated conditions. Gene mapping and protein analysis together with complementation assays showed that a protein related to SecA, which is a component of the Sec protein secretion system in a wide range of bacteria, is needed at least for the production of the BauA acinetobactin outer membrane receptor. Furthermore, this derivative was unable to use hemin as an iron source under limiting conditions. Taken together, these results indicate that A. baumannii expresses siderophore-mediated and hemin acquisition functions, although different isolates differ in their iron acquisition capacity. Unexpectedly, the ability of this pathogen to acquire iron depends on the expression of a SecA protein secretion function, which has not been associated with iron acquisition in bacteria.
1 Communities
0 Members
0 Resources
9 MeSH Terms