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

doi:10.1016/j.chom.2021.08.012

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 journal › Article › peer-review

10 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 language	English (US)
Pages (from-to)	1531-1544.e9
Journal	Cell Host and Microbe
Volume	29
Issue number	10
DOIs	https://doi.org/10.1016/j.chom.2021.08.012
State	Published - 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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10.1016/j.chom.2021.08.012

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title = "Systematic reconstruction of an effector-gene network reveals determinants of Salmonella cellular and tissue tropism",

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.",

keywords = "SPI-2 T3SS, Salmonella Typhimurium, bacterial pathogenesis, effector proteins, sifA, sopD2, spv locus, sseF, sseG, steA",

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

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year = "2021",

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doi = "10.1016/j.chom.2021.08.012",

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AU - Chen, Didi

AU - Burford, Wesley B.

AU - Pham, Giang

AU - Zhang, Lishu

AU - Alto, Laura T.

AU - Ertelt, James M.

AU - Winter, Maria G.

AU - Winter, Sebastian E.

AU - Way, Sing Sing

AU - Alto, Neal M.

PY - 2021/10/13

Y1 - 2021/10/13

N2 - 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.

AB - 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.

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KW - Salmonella Typhimurium

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KW - effector proteins

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KW - sseG

KW - steA

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

Abstract

Keywords

ASJC Scopus subject areas

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