Dual spatial host-bacterial gene expression in Mycobacterium abscessus respiratory infections

Commun Biol. 2024 Oct 9;7(1):1287. doi: 10.1038/s42003-024-06929-5.

Abstract

Co-localization of spatial transcriptome information of host and pathogen can revolutionize our understanding of microbial pathogenesis. Here, we aimed to demonstrate that customized bacterial probes can be successfully used to identify host-pathogen interactions in formalin-fixed-paraffin-embedded (FFPE) tissues by probe-based spatial transcriptomics technology. We analyzed the spatial gene expression of bacterial transcripts with the host transcriptomic profile in murine lung tissue chronically infected with Mycobacterium abscessus embedded in agar beads. Customized mycobacterial probes were designed for the constitutively expressed rpoB gene (an RNA polymerase β subunit) and the virulence factor precursor lsr2, modulated by oxidative stress. We found a correlation between the rpoB expression, bacterial abundance in the airways, and an increased expression of lsr2 virulence factor in lung tissue with high oxidative stress. Overall, we demonstrate the potential of dual bacterial and host gene expression assay in FFPE tissues, paving the way for the simultaneous detection of host and bacterial transcriptomes in pathological tissues.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Bacterial
  • Host-Pathogen Interactions* / genetics
  • Lung / microbiology
  • Mice
  • Mycobacterium Infections, Nontuberculous* / genetics
  • Mycobacterium Infections, Nontuberculous* / microbiology
  • Mycobacterium abscessus* / genetics
  • Respiratory Tract Infections / genetics
  • Respiratory Tract Infections / microbiology
  • Transcriptome
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Virulence Factors
  • DNA-Directed RNA Polymerases
  • RNA polymerase beta subunit