H-NS Mediates the Silencing of Laterally Acquired Genes in Bacteria

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Abstract
Histone-like nucleoid structuring protein (H-NS) is a modular protein that is associated with the bacterial nucleoid. We used chromatin immunoprecipitation to determine the binding sites of H-NS and RNA polymerase on the Salmonella enterica serovar Typhimurium chromosome. We found that H-NS does not bind to actively transcribed genes and does not co-localize with RNA polymerase. This shows that H-NS principally silences gene expression by restricting the access of RNA polymerase to the DNA. H-NS had previously been shown to preferentially bind to curved DNA in vitro. In fact, at the genomic level we discovered that the level of H-NS binding correlates better with the AT-content of DNA. This is likely to have evolutionary consequences because we show that H-NS binds to many Salmonella genes acquired by lateral gene transfer, and functions as a gene silencer. The removal of H-NS from the cell causes un-controlled expression of several Salmonella pathogenicity islands, and we demonstrate that this has deleterious consequences for bacterial fitness. Our discovery of this novel role for H-NS may have implications for the acquisition of foreign genes by enteric bacteria. In recent decades, gene silencing has been well-characterised in plants and animals, and involves the prevention of transcription by DNA-methylation and histone-modification, or interference with translation by small RNA molecules. This issue of PLoS Pathogens reports the discovery that global gene silencing also occurs in bacteria. The novel mechanism is mediated by the highly abundant histone-like nucleoid structuring protein (H-NS), which blocks the expression of 254 genes in wild-type Salmonella. Many of these genes were acquired through horizontal gene transfer, including pathogenicity islands, and these are silenced by the binding of H-NS to AT-rich chromosomal regions. The study reveals that H-NS prevents the uncontrolled transcription of genes within pathogenicity islands to ensure that bacterial fitness is maintained. It is suggested that H-NS plays a role in bacterial evolution by influencing both the acquisition and maintenance of foreign DNA.