SspA is required for acid resistance in stationary phase by downregulation of H-NS in Escherichia coli.

The stringent starvation protein A (SspA) is a RNA polymerase-associated protein and is required for transcriptional activation of bacteriophage P1 late promoters. However, the role of SspA in gene expression in Escherichia coli is essentially unknown. In this work, we show that SspA is essential for cell survival during acid-induced stress. Apparently, SspA inhibits stationary-phase accumulation of H-NS, a global regulator which functions mostly as a repressor, thereby derepressing multiple stress defence systems including those for acid stress and nutrient starvation. Consequently, the gene expression pattern of the H-NS regulon is altered in the sspA mutant, leading to acid-sensitive and hypermotile phenotypes. Thus, our study indicates that SspA is a global regulator, which acts upstream of H-NS, and thereby plays an important role in the stress response of E. coli during stationary phase. In addition, our results indicate that the expression of the H-NS regulon is sensitive to small changes in the cellular level of H-NS, enabling the cell to response rapidly to environment cues. As SspA and H-NS are highly conserved among Gram-negative bacteria, of which many are pathogenic, the global role of SspA in the stress response and pathogenesis is discussed.