Mapping and regulation of genes within Salmonella pathogenicity island 12 that contribute to in vivo fitness of Salmonella enterica Serovar Typhimurium

Salmonella pathogenicity island 12 (SPI-12) of Salmonella enterica serovar Typhimurium is a 15-kb region that encompasses genes STM2230 to STM2245 and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experiments, quantitative reverse transcription-PCR (RT-PCR), and immunoblotting demonstrated that the virulence regulator SsrB and STM2239 contribute to transcriptional activation of genes in SPI-12. SsrB was found to indirectly regulate this locus by transcriptional read-through from the sspH2 (STM2241) promoter. Chromatin immunoprecipitation showed that STM2239 copurified with the promoter regulating STM2237, suggesting that STM2239 may function as an antiterminator to activate adjacent genes. These results demonstrate that bacteriophage genes may be adapted by pathogenic bacteria to improve fitness in the host.