Systematic reconstruction of an effector-gene network reveals determinants of Salmonella cellular and tissue tropism

Didi Chen, Wesley B. Burford, Giang Pham, Lishu Zhang, Laura T. Alto, James M. Ertelt, Maria G. Winter, Sebastian E. Winter, Sing Sing Way, Neal M. Alto

Research output: Contribution to journalArticlepeer-review

Abstract

The minimal genetic requirements for microbes to survive within multiorganism communities, including host-pathogen interactions, remain poorly understood. Here, we combined targeted gene mutagenesis with phenotype-guided genetic reassembly to identify a cooperative network of SPI-2 T3SS effector genes that are sufficient for Salmonella Typhimurium (STm) to cause disease in a natural host organism. Five SPI-2 effector genes support pathogen survival within the host cell cytoplasm by coordinating bacterial replication with Salmonella-containing vacuole (SCV) division. Unexpectedly, this minimal genetic repertoire does not support STm systemic infection of mice. In vivo screening revealed a second effector-gene network, encoded by the spv operon, that expands the life cycle of STm from growth in cells to deep-tissue colonization in a murine model of typhoid fever. Comparison between Salmonella infection models suggests how cooperation between effector genes drives tissue tropism in a pathogen group.

Original languageEnglish (US)
Pages (from-to)1531-1544.e9
JournalCell Host and Microbe
Volume29
Issue number10
DOIs
StatePublished - Oct 13 2021

Keywords

  • SPI-2 T3SS
  • Salmonella Typhimurium
  • bacterial pathogenesis
  • effector proteins
  • sifA
  • sopD2
  • spv locus
  • sseF
  • sseG
  • steA

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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