UBC Theses and Dissertations
Rifampicin induced transcription modulation in salmonella enterica serovar typhimurium Yim, Grace
Sub-inhibitory concentrations of antibiotics modulate global transcription patterns in bacteria. Genes involved in stress responses, metabolism, virulence, motility and other functions have been identified as being activated or repressed in response to rifampicin by screening a promoter-/wx library of 6528 clones in Salmonella enterica serovar Typhimurium (S. typhimurium) 14028. Rifampicin differentially regulates the transcription of S. typhimurium virulence genes. Transcription of genes involved in intracellular growth, survival and replication in macrophages was up-regulated. Motility genes and genes associated with intestinal invasion, SPI-1 and its secreted effectors, were transcriptionally down-regulated by rifampicin. Rifampicin induced transcription modulation in a concentration dependent manner with differential responses as great as 200 fold in some cases. Testing of eight rifampicin responsive promoters.in one of six S. typhimurium 14028 regulatory protein and sigma factor mutants: crp,fnr, ihfB,fis, hns and rpoS showed that for most of the promoter-mutant combinations rifampicin induced transcription modulation (RITM) was independent of the regulators. In a few cases, RITM did appear to depend on the factor tested and in those cases the altered protein may work co-operatively with other unidentified regulatory mechanisms to cause RITM of the tested promoter. However, no single regulator tested affected RITM for all promoters suggesting that different mechanisms may elicit RITM and RITM may be promoter dependent. Possible mechanisms will be discussed. Rifampicin induced changes in regulatory proteins or RNA polymerase may mimic intestinal cues that promote switching of virulence modes from penetration of epithelial cells to intracellular survival and proliferation.
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