Research ArticleInfection

Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions

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Science Translational Medicine  14 Mar 2018:
Vol. 10, Issue 432, eaan6361
DOI: 10.1126/scitranslmed.aan6361

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Imaging infection

There are many reagents and assays to test samples for bacterial infections, but detecting pathogens at an early stage within intact tissue is challenging. Cassat et al. developed an imaging platform that detected changes in proteins and elements within murine host tissue after infection with Staphylococcus aureus. The imaging method was based on the known competition for nutrient metal between pathogens and host. Using bioluminescent imaging, blockface imaging, and magnetic resonance imaging coupled with matrix-assisted laser desorption/ionization imaging mass spectrometry and laser ablation inductively coupled plasma mass spectrometry, the imaging platform identified regions of metal starvation within abscesses. This multimodal imaging platform could help advance our understanding of inflammatory response and host-pathogen interactions during infection.

Abstract

Diseases are characterized by distinct changes in tissue molecular distribution. Molecular analysis of intact tissues traditionally requires preexisting knowledge of, and reagents for, the targets of interest. Conversely, label-free discovery of disease-associated tissue analytes requires destructive processing for downstream identification platforms. Tissue-based analyses therefore sacrifice discovery to gain spatial distribution of known targets or sacrifice tissue architecture for discovery of unknown targets. To overcome these obstacles, we developed a multimodality imaging platform for discovery-based molecular histology. We apply this platform to a model of disseminated infection triggered by the pathogen Staphylococcus aureus, leading to the discovery of infection-associated alterations in the distribution and abundance of proteins and elements in tissue in mice. These data provide an unbiased, three-dimensional analysis of how disease affects the molecular architecture of complex tissues, enable culture-free diagnosis of infection through imaging-based detection of bacterial and host analytes, and reveal molecular heterogeneity at the host-pathogen interface.

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