Integration host factor alleviates H-NS silencing of the Salmonella enterica serovar Typhimurium master regulator of SPI1, hilA

Abstract

Coordination of the expression of Salmonella enterica invasion genes on Salmonella pathogenicity island 1 (SPI1) depends on a complex circuit involving several regulators that converge on expression of the hilA gene, which encodes a transcriptional activator (HilA) that modulates expression of the SPI1 virulence genes. Two of the global regulators that influence hilA expression are the nucleoid-associated proteins Hha and H-NS. They interact and form a complex that modulates gene expression. A chromosomal transcriptional fusion was constructed to assess the effects of these modulators on hilA transcription under several environmental conditions as well as at different stages of growth. The results obtained showed that these proteins play a role in silencing hilA expression at both low temperature and low osmolarity, irrespective of the growth phase. H-NS accounts for the main repressor activity. At high temperature and osmolarity, H-NS-mediated silencing completely ceases when cells enter the stationary phase, and hilA expression is induced. Mutants lacking IHF did not induce hilA in cells entering the stationary phase, and this lack of induction was dependent on the presence of H-NS. Band-shift assays and in vitro transcription data showed that for hilA induction under certain growth conditions, IHF is required to alleviate H-NS-mediated silencing.

Interaction of the Histone-Like Nucleoid Structuring Protein and the General Stress Response Regulator RpoS at Vibrio cholerae Promoters That Regulate Motility and Hemagglutinin/Protease Expression

“…Thus, we suggest that RpoS could diminish H-NS occupancy indirectly by inducing the expression of other trans-acting transcriptional regulators. IHF is known to alleviate H-NS silencing of S. enterica hilA (43), E. coli csgD (38), Shigella flexneri vir genes (41), and the bacteriophage Mu early promoter (56). In V. cholerae, IHF positively affects tcpA expression by binding to its promoter at a position that overlaps the H-NS binding site (52).…”

The Different Strategies Used by Salmonella to Invade Host Cells

“…Each of them binds directly to the hilA promoter and is able to activate its own expression. In fact, HilC, HilD and probably RtsA, act as derepressors of hilA transcription by counteracting the silencing exerted by nucleoidstructuring proteins such as H-NS or Hha (Akbar et al, 2003;Queiroz et al, 2011). The reason why HilC, HilD and RtsA play such an important role in T3SS-1 expression through hilA regulation is that they are at the integration point of a lot of signals that control SPI-1 expression ( Figure 4).…”

Regulation of Bacterial Virulence by Csr (Rsm) Systems

“…Similar to IHF, H-NS also affects DNA architecture, and it is known to repress gene expression under conditions of low temperature or low osmolarity (189). While the conditions that control MvaT/MvaU activity are unknown, IHF antagonizes H-NS-dependent silencing of gene expression in bacterial pathogens, including E. coli, V. cholerae, and S. enterica (190)(191)(192). Further studies are needed to determine whether IHF antagonizes MvaT/MvaU-dependent repression of RsmZ.…”