Visualizing Staphylococcus aureus pathogenic membrane modification within the host infection environment by multimodal imaging mass spectrometry

William J. Perry, Caroline M. Grunenwald, Raf Van de Plas, James C. Witten, Daniel R. Martin, Suneel S. Apte, James E. Cassat, Gösta B. Pettersson, Richard M. Caprioli, Eric P. Skaar*, Jeffrey M. Spraggins*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)
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Abstract

Bacterial pathogens have evolved virulence factors to colonize, replicate, and disseminate within the vertebrate host. Although there is an expanding body of literature describing how bacterial pathogens regulate their virulence repertoire in response to environmental signals, it is challenging to directly visualize virulence response within the host tissue microenvironment. Multimodal imaging approaches enable visualization of host-pathogen molecular interactions. Here we demonstrate multimodal integration of high spatial resolution imaging mass spectrometry and microscopy to visualize Staphylococcus aureus envelope modifications within infected murine and human tissues. Data-driven image fusion of fluorescent bacterial reporters and matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry uncovered S. aureus lysyl-phosphatidylglycerol lipids, localizing to select bacterial communities within infected tissue. Absence of lysyl-phosphatidylglycerols is associated with decreased pathogenicity during vertebrate colonization as these lipids provide protection against the innate immune system. The presence of distinct staphylococcal lysyl-phosphatidylglycerol distributions within murine and human infections suggests a heterogeneous, spatially oriented microbial response to host defenses.

Original languageEnglish
Pages (from-to)1209-1217.e4
JournalCell Chemical Biology
Volume29
Issue number7
DOIs
Publication statusPublished - 2022

Bibliographical note

Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care
Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.

Keywords

  • host-pathogen interactions
  • image fusion
  • imaging mass spectrometry
  • infectious disease
  • infective endocarditis
  • MALDI imaging
  • multimodal imaging
  • staph infection
  • Staphylococcus aureus

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