The Sfh protein is encoded by self-transmissible plasmids involved in human typhoid and is closely related to the global regulator H-NS. We have found that Sfh provides a stealth function that allows the plasmids to be transmitted to new bacterial hosts with minimal effects on their fitness. Introducing the plasmid without the sfh gene imposes a mild H-NS(-) phenotype and a severe loss of fitness due to titration of the cellular pool of H-NS by the A+T-rich plasmid. This stealth strategy seems to be used widely to aid horizontal DNA transmission and has important implications for bacterial evolution.
Shigella flexneri 2a is known to express the H-NS nucleoid-structuring protein and the paralogous protein StpA. Using bioinformatic analysis we have now discovered a third member of the H-NS protein family, Sfh (Shigella flexneri H-NS-like protein), in strain 2457T. This protein is encoded by the sfh gene, which is located on a high-molecular-mass plasmid that is closely related to the self-transmissible plasmid R27. When expressed in Escherichia coli, the Sfh protein can complement an hns null mutation, restoring wild-type Bgl, porin protein, and mucoidy phenotypes, and wild-type expression of the fliC and proU genes. While a knockout mutation in the sfh gene alone had no effect on the expression of virulence genes in S. flexneri, an additive effect on virulence gene derepression was seen when the sfh lesion was combined with a mutation in hns. Over-expression of the sfh gene repressed expression of the VirB virulence regulatory protein and transcription of a VirB-dependent structural gene promoter. The purified Sfh protein bound specifically to DNA sequences containing the promoters of the virF and virB virulence regulatory genes. These findings show that Sfh has the ability to influence genetic events beyond the genetic element that encodes it, including the expression of the S. flexneri virulence genes. They raise the possibility of a triangular relationship among three closely related proteins with broad consequences for genetic events in the bacterium that harbours them.
ELB-21 kills S. aureus by forming multiple interstrand and intrastrand DNA cross-links, resulting in induction of the DNA damage response, derepression of resident prophages and modulation of a limited number of genes involved with cell wall synthesis.
The IncHI1 self-transmissible plasmid pSf-R27 from Shigella flexneri 2a strain 2457T harbors sfh, a gene that codes for a protein with strong amino acid sequence homology to the global transcription regulator and nucleoid-associated protein H-NS and to its paralogue, StpA. Previously, we discovered that the expression of sfh mRNA is growth phase dependent such that in cultures growing in Lennox broth at 37°C, the transcript is readily detectable in the early stages of exponential growth but is not detectable at the onset of stationary phase. In contrast, the Sfh protein is poorly expressed in early-exponential growth when sfh mRNA is abundant whereas it is expressed to a high level in early stationary phase, when sfh transcript expression is low (P. Deighan, C. Beloin, and C. J. Dorman, Mol. Microbiol. 48:1401-1416, 2003). This unusual pattern of reciprocal mRNA and protein expression is not due to growth phase-dependent effects on either mRNA or protein stability, nor is it due to the known abilities of the Sfh, StpA, and H-NS proteins to influence sfh gene expression. Instead, our data point to a blockade of sfh mRNA translation in early-exponential growth that is relieved as the culture enters the stationary phase of growth. Replacing the 5 end and translation initiation signals of the sfh mRNA with heterologous sequences did not alter the growth phase-dependent expression of the Sfh protein, suggesting that growth phase control of translation is intrinsic to another component of the message.
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