Topologically correct synthetic reconstruction of pathogen social behavior found during yersinia growth in deep tissue sites

Stacie A. Clark, Derek Thibault, Lauren M. Shull, Kimberly M. Davis, Emily Aunins, Tim van Opijnen, Ralph Isberg

Research output: Contribution to journalArticlepeer-review

Abstract

Within deep tissue sites, extracellular bacterial pathogens often replicate in clusters that are surrounded by immune cells. Disease is modulated by interbacterial interactions as well as bacterial-host cell interactions resulting in microbial growth, phagocytic attack and secretion of host antimicrobial factors. To overcome the limited ability to manipulate these infection sites, we established a system for Yersinia pseudotuberculosis (Yptb) growth in microfluidics-driven microdroplets that regenerates microbial social behavior in tissues. Chemical generation of nitric oxide (NO) in the absence of immune cells was sufficient to reconstruct microbial social behavior, as witnessed by expression of the NO-inactivating protein Hmp on the extreme periphery of microcolonies, mimicking spatial regulation in tissues. Similarly, activated macrophages that expressed inducible NO synthase (iNOS) drove peripheral expression of Hmp, allowing regeneration of social behavior observed in tissues. These results argue that topologically correct microbial tissue growth and associated social behavior can be reconstructed in culture.

Original languageEnglish (US)
Article numbere58106
Pages (from-to)1-20
Number of pages20
JournaleLife
Volume9
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Topologically correct synthetic reconstruction of pathogen social behavior found during yersinia growth in deep tissue sites'. Together they form a unique fingerprint.

Cite this