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Single-Cell Mass Spectrometry Enables Insight into Heterogeneity in Infectious Disease

Tra D Nguyen1, Yunpeng Lan1, Shelley S Kane1

  • 1Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.

Analytical Chemistry
|July 21, 2022
PubMed

Insights

Cellular metabolism varies in host cells during Trypanosoma cruzi infection, impacting Chagas disease. Uninfected cells near infected ones also show metabolic changes, revealing new insights into disease.

Area of Science:

  • Infectious Diseases
  • Cellular Metabolism
  • Host-Pathogen Interactions

Background:

  • Cellular heterogeneity is often overlooked in infectious diseases, including Chagas disease (CD).
  • Trypanosoma cruzi (T. cruzi) exhibits heterogeneity in replication and drug susceptibility.
  • The role of metabolic heterogeneity in host cells during T. cruzi infection remains unexplored.

Purpose of the Study:

  • To investigate host cell metabolic heterogeneity during T. cruzi infection.
  • To apply a novel single-cell mass spectrometry (SCMS) method for metabolomics analysis in infected cells.
  • To understand the impact of T. cruzi on host cell metabolism and adjacent cells.

Main Methods:

  • Development of a Single-probe SCMS method compatible with biosafety protocols.
  • Acquisition of metabolomics data from individual host cells during T. cruzi infection in vitro.
  • Comparative analysis of metabolic profiles between infected, uninfected, and control cells.

Main Results:

  • Demonstrated significant heterogeneity in the metabolic response of host cells to T. cruzi infection.
  • Identified divergent metabolic profiles in parasite-infected cells compared to control cells.
  • Observed metabolic impacts in uninfected cells adjacent to infected cells, with notable increases in glycerophospholipids.

Conclusions:

  • Host cell metabolic heterogeneity plays a role in the pathogenesis of Chagas disease.
  • The study provides novel insights into host-parasite interactions at the metabolic level.
  • This work represents the first bioanalytical SCMS application for studying mammalian-infectious agents, with broad potential for infectious disease research.

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