Integrated molecular imaging reveals tissue heterogeneity driving host-pathogen interactions.

Cassat JE, Moore JL, Wilson KJ, Stark Z, Prentice BM, Van de Plas R, Perry WJ, Zhang Y, Virostko J, Colvin DC, Rose KL, Judd AM, Reyzer ML, Spraggins JM, Grunenwald CM, Gore JC, Caprioli RM, Skaar EP
Sci Transl Med. 2018 10 (432)

PMID: 29540616 · PMCID: PMC6005374 · DOI:10.1126/scitranslmed.aan6361

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 , 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.

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

MeSH Terms (10)

Animals Female Host-Pathogen Interactions Magnetic Resonance Imaging Mass Spectrometry Mice Mice, Inbred BALB C Molecular Imaging Staphylococcal Infections Staphylococcus aureus

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