Bacterial pathogens are rapidly gaining resistance to antimicrobial therapeutics undermining the ability of modern medicine to treat such infections [1,2]. The Centers for Disease Control and Prevention reported over 2 million people in the United States become infected with drug-resistant bacteria annually, causing at least 23,000 deaths [3]. In light of such reports, the need to identify and study novel targets for antimicrobial intervention using emerging analytical technologies is paramount for the future successful treatment of infectious diseases. One potential target for antimicrobial therapeutics involves transition metal homeostasis at the pathogen-host interface [4,5]. Metals are an essential component of biological function for all cells. It is estimated that 30-45% of all enzymes utilize a transition metal cofactor to enhance catalysis and reactivity [6,7]. Therefore, bacterial pathogens proliferating within a host must obtain metals to survive and grow, causing disease. In response, hosts seek to sequester these elements from pathogens, a process known as nutritional immunity [4,8]. With a more detailed understanding of host mechanisms of metal sequestration and bacterial mechanisms of metal scavenging, novel therapeutic targets can be discovered. S. aureus is a Gram-positive pathogen that commensally colonizes the anterior nares of an estimated 25% of the human population [9]. To cause disease, S. aureus breaches the initial site of infection and enters the bloodstream where it can cause infectious lesions on virtually any organ [10]. A hallmark of these purulent infectious foci, called abscesses, is the recruitment of host immune cells, including neutrophils and macrophages, which generate oxidative stress in an attempt to kill the pathogen [11,12]. Abscess formation has been studied extensively using histologically methods [10,13,14]; however, a molecular understanding of organ-specific heterogeneity of bacterial virulence factor expression and host response is not yet understood.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103391-08
Application #
9417028
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
965717143
City
Nashville
State
TN
Country
United States
Zip Code
37240
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Ryan, Daniel J; Nei, David; Prentice, Boone M et al. (2018) Protein identification in imaging mass spectrometry through spatially targeted liquid micro-extractions. Rapid Commun Mass Spectrom 32:442-450
Daniels, Anthony B; Froehler, Michael T; Pierce, Janene M et al. (2018) Pharmacokinetics, Tissue Localization, Toxicity, and Treatment Efficacy in the First Small Animal (Rabbit) Model of Intra-Arterial Chemotherapy for Retinoblastoma. Invest Ophthalmol Vis Sci 59:446-454
Grove, Kerri J; Lareau, Nichole M; Voziyan, Paul A et al. (2018) Imaging mass spectrometry reveals direct albumin fragmentation within the diabetic kidney. Kidney Int 94:292-302
Ryan, Daniel J; Spraggins, Jeffrey M; Caprioli, Richard M (2018) Protein identification strategies in MALDI imaging mass spectrometry: a brief review. Curr Opin Chem Biol 48:64-72
Covington, Brett C; Spraggins, Jeffrey M; Ynigez-Gutierrez, Audrey E et al. (2018) Response of Hypogean Actinobacterial Genera Secondary Metabolism to Chemical and Biological Stimuli. Appl Environ Microbiol :
Stark, David T; Anderson, David M G; Kwong, Jacky M K et al. (2018) Optic Nerve Regeneration After Crush Remodels the Injury Site: Molecular Insights From Imaging Mass Spectrometry. Invest Ophthalmol Vis Sci 59:212-222
Noble, Kenyaria V; Reyzer, Michelle L; Barth, Jeremy L et al. (2018) Use of Proteomic Imaging Coupled With Transcriptomic Analysis to Identify Biomolecules Responsive to Cochlear Injury. Front Mol Neurosci 11:243
Yang, Bo; Patterson, Nathan Heath; Tsui, Tina et al. (2018) Single-Cell Mass Spectrometry Reveals Changes in Lipid and Metabolite Expression in RAW 264.7 Cells upon Lipopolysaccharide Stimulation. J Am Soc Mass Spectrom 29:1012-1020
Soto, Marion; Orliaguet, Lucie; Reyzer, Michelle L et al. (2018) Pyruvate induces torpor in obese mice. Proc Natl Acad Sci U S A 115:810-815

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