Mapping Molecular Interactions in the Clostridioides difficile Infected Gastrointestinal Tract Using Multimodal Imaging Mass Spectrometry

Author(s):  
Emma R. Guiberson ◽  
Aaron G. Wexler ◽  
William J. Perry ◽  
Eric P. Skaar ◽  
Richard M. Caprioli ◽  
...  
2021 ◽  
Author(s):  
Emma R. Guiberson ◽  
Aaron G. Wexler ◽  
Christopher J. Good ◽  
Eric P. Skaar ◽  
Jeffrey M. Spraggins ◽  
...  

ABSTRACTDigestive diseases impact 62 million people a year in the United States. Despite the central role of the gut to human health, past imaging mass spectrometry (IMS) investigations into the gastrointestinal tract are incomplete. The gastrointestinal tract, including luminal content, harbors a complex mixture of microorganisms, host dietary content, and immune factors. Existing imaging approaches remove luminal content, and images focus on small regions of tissue. Here, we demonstrate the use of a workflow to collect multimodal imaging data for both intestinal tissue and luminal content. This workflow for matrix-assisted laser desorption/ionization imaging mass spectrometry retains luminal content and expands the amount of tissue imaged on one slide. Results comparing tissue and luminal content show unique molecular distributions using multimodal imaging modalities including protein, lipid, and elemental imaging. Leveraging this method to investigate intestinal tissue infected with Clostridioides difficile compared to control tissue shows clear differences in lipid abundance of various lipid classes in luminal content during infection. These data highlight the potential for this approach to detect unique biological and markers of infection in the gut.


2020 ◽  
Vol 31 (12) ◽  
pp. 2401-2415
Author(s):  
Elizabeth K. Neumann ◽  
Katerina V. Djambazova ◽  
Richard M. Caprioli ◽  
Jeffrey M. Spraggins

2019 ◽  
Vol 116 (44) ◽  
pp. 21980-21982 ◽  
Author(s):  
William J. Perry ◽  
Jeffrey M. Spraggins ◽  
Jessica R. Sheldon ◽  
Caroline M. Grunenwald ◽  
David E. Heinrichs ◽  
...  

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 Staphylococcus aureus siderophores across infectious foci, challenging the paradigm that the vertebrate host is a uniformly iron-depleted environment to invading microbes.


2014 ◽  
Vol 46 (S1) ◽  
pp. 375-378 ◽  
Author(s):  
Jörg Hanrieder ◽  
Oskar Karlsson ◽  
Eva B. Brittebo ◽  
Per Malmberg ◽  
Andrew G. Ewing

2020 ◽  
Author(s):  
Elizabeth Neumann ◽  
Lukasz Migas ◽  
Jamie L. Allen ◽  
Richard Caprioli ◽  
Raf Van de Plas ◽  
...  

<div> <div> <p>Small metabolites are essential for normal and diseased biological function but are difficult to study because of their inherent structural complexity. MALDI imaging mass spectrometry (IMS) of small metabolites is particularly challenging as MALDI matrix clusters are often isobaric with metabolite ions, requiring high resolving power instrumentation or derivatization to circumvent this issue. An alternative to this is to perform ion mobility separation before ion detection, enabling the visualization of metabolites without the interference of matrix ions. Here, we use MALDI timsTOF IMS to image small metabolites at high spatial resolution within the human kidney. Through this, we have found metabolites, such as arginic acid, acetylcarnitine, and choline that localize to the cortex, medulla, and renal pelvis, respectively. We have also demonstrated that trapped ion mobility spectrometry (TIMS) can resolve matrix peaks from metabolite signal and separate both isobaric and isomeric metabolites with different localizations within the kidney. The added ion mobility data dimension dramatically increased the peak capacity for molecular imaging experiments. Future work will involve further exploring the small metabolite profiles of human kidneys as a function of age, gender, and ethnicity.</p></div></div>


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