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Infectious Disease

Research Partner

Eric Skaar, Ph.D. M.P.H., Vanderbilt University, Dept. of Pathology, Microbiology, and Immunology

The focus of this work is to identify and functionally characterize systems involved in metal trafficking and metabolism when a pathogen is within a host or living in a biofilm community, with the long-term goal of identifying novel targets for therapeutic intervention against bacterial pathogens. IMS experiments revealed distinct differences in calprotectin (S100A8 and S100A9) and trace metal distributions between Staphylococus aureus infected and control mouse kidney sections (Figure 1) [1] and in a murine model of Acinetobacter baumannii pneumonia [2,3]. Advances in spatial resolution allowed the unprecedented molecular examination of abscesses and showed heterogeneities within the abscess centers, where staphylococcal colonies were found. Biofilms of Pseudomonas aeruginosa were also imaged and metal gradients were correlated  with specific protein distributions. These findings will pioneer a path toward understanding how bacterial communities respond to alterations in metal availability and ultimately to improved clinical care [4].

Metals.jpg

Figure 1. Calprotectin (S100A8 and S100A9) and trace metal distributions inStaphylococus aureus infected and control mouse kidney sections. Modified from: Infect Immun 81 (9):3395-405.


Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions

Integrating bioluminescence imaging of bacteria guides MALDI IMS data collection to regions where bacteria are actively causing disease, providing molecular insight at the pathogen-host interface.

Cassat et al., Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions. Sci Transl Med, 2018 [5]


Dietary Manganese Promotes Staphylococcal Infection of the Heart

Juttukonda et al., Dietary Manganese Promotes Staphylococcal Infection of the Heart. Cell Host Microbe, 2017 [6]

Mice fed a diet high in manganese show increased Staphylococcal colonization of heart, hallmarked by an increase in the manganese-binding protein complex calprotectin, whose subunit S100A8 is analyzed by MALDI IMS.

 


References

1. Kehl-Fie TE, Zhang Y, Moore JL, Farrand AJ, Hood MI, Rathi S, Chazin WJ, Caprioli RM, Skaar EP (2013) MntABC and MntH contribute to systemic Staphylococcus aureus infection by competing with calprotectin for nutrient manganese. Infect Immun 81 (9):3395-3405. PMCID: 3754211. Return to text.

2. Hood MI, Mortensen BL, Moore JL, Zhang Y, Kehl-Fie TE, Sugitani N, Chazin WJ, Caprioli RM, Skaar EP (2012) Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS pathogens 8 (12):e1003068. PMCID: 3516566. Return to text.

3. Moore JL, Becker KW, Nicklay JJ, Boyd KL, Skaar EP, Caprioli RM (2014) Imaging mass spectrometry for assessing temporal proteomics: analysis of calprotectin in Acinetobacter baumannii pulmonary infection. Proteomics 14 (7-8):820-828. PMCID: 3883928. Return to text.

4. Moore JL, Caprioli RM, Skaar EP (2014) Advanced mass spectrometry technologies for the study of microbial pathogenesis. Curr Opin Microbiol 19:45-51. PMCID: 4125470. Return to text.

5. Cassat JE, Caprioli RM, Skaar EP (2018) Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions. Sri Transl Med 2018 Mar 14;10(432). pii: eaan6361. doi: 10.1126/scitranslmed.aan6361

6. Chazin WJ, Caprioli RM, Skaar EP (2017) Dietary Manganese Promotes Staphylococcal Infection of the Heart Cell Host Microbe 2017 Oct 11;22(4):531-542.e8. doi: 10.1016/j.chom.2017.08.009. Epub 2017 Sep 21