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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.

SUBMITTER: Chen D 

PROVIDER: S-EPMC8516738 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Chen Didi D   Burford Wesley B WB   Pham Giang G   Zhang Lishu L   Alto Laura T LT   Ertelt James M JM   Winter Maria G MG   Winter Sebastian E SE   Way Sing Sing SS   Alto Neal M NM  

Cell host & microbe 20210917 10


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  ...[more]

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