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 A Alto, James M. Ertelt, Maria G. Winter, Sebastian E. Winter, Sing Sing Way, Neal M. Alto

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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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