Silencing of xenogeneic DNA by H-NS—facilitation of lateral gene transfer in bacteria by a defense system that recognizes foreign DNA

Abstract

Lateral gene transfer has played a prominent role in bacterial evolution, but the mechanisms allowing bacteria to tolerate the acquisition of foreign DNA have been incompletely defined. Recent studies show that H-NS, an abundant nucleoid-associated protein in enteric bacteria and related species, can recognize and selectively silence the expression of foreign DNA with higher adenine and thymine content relative to the resident genome, a property that has made this molecule an almost universal regulator of virulence determinants in enteric bacteria. These and other recent findings challenge the ideas that curvature is the primary determinant recognized by H-NS and that activation of H-NS-silenced genes in response to environmental conditions occurs through a change in the structure of H-NS itself. Derepression of H-NS-silenced genes can occur at specific promoters by several mechanisms including competition with sequence-specific DNA-binding proteins, thereby enabling the regulated expression of foreign genes. The possibility that microorganisms maintain and exploit their characteristic genomic GC ratios for the purpose of self/non-self-discrimination is discussed.

Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes inMycobacterium tuberculosis

“…It has been postulated that H-NS may undergo structural and functional alteration under these environmental conditions (2, 11); however, the correlation between the observed structural changes with H-NS-dependent gene expression has been less than perfect (10,11). Instead, it was recently proposed that the primary role of H-NS is to silence AT-rich DNA, presumably as a mechanism of defense against foreign sequences (10). In E. coli and Salmonella, silencing is the "default" state, and the repression is relieved only when H-NS is displaced from the gene by some alterations in nucleoid structure or competition by a binding factor (10).…”

“…Although many H-NS repressed genes are regulated by environmental conditions such as pH, osmolarity, and growth temperature, expression of H-NS appears to be relatively constant under a range of environmental conditions (51,52), suggesting that gene regulation by H-NS is not mediated by a change in the protein abundance. It has been postulated that H-NS may undergo structural and functional alteration under these environmental conditions (2, 11); however, the correlation between the observed structural changes with H-NS-dependent gene expression has been less than perfect (10,11). Instead, it was recently proposed that the primary role of H-NS is to silence AT-rich DNA, presumably as a mechanism of defense against foreign sequences (10).…”

“…Instead, it was recently proposed that the primary role of H-NS is to silence AT-rich DNA, presumably as a mechanism of defense against foreign sequences (10). In E. coli and Salmonella, silencing is the "default" state, and the repression is relieved only when H-NS is displaced from the gene by some alterations in nucleoid structure or competition by a binding factor (10). Within this context, it is not surprising that an "H-NS-like" molecule exists in mycobacteria and related actinomycetes, which are characterized by the high GC content of their genomes (∼70%).…”

“…High-affinity binding sites have also been reported with the current paradigm because they serve as initiation sites for nucleation of H-NS to form higher-order nucleoprotein structures (6). H-NS is responsible for binding and repressing >400 genes in Salmonella (4, 7) and in Escherichia coli (8,9), many of which are DNA sequences obtained through horizontal gene transfer and involved in adaptive stress responses and virulence (10). Numerous phenotypes associated with hns mutations have been described, and the effects of H-NS on gene expression are largely inhibitory (2,11), which is partially explained by the ability of H-NS to bridge adjacent helices of DNA (12,13), causing either the trapping or the occlusion of RNA polymerase in the promoter regions (2,14).…”

Lateral genetic transfer: open issues

“…Thus, lateral genes that survive the initial 'churn' can slowly become better integrated into host-cell networks, e.g. by recruiting transcriptional regulators (Navarre et al 2007;Wellner et al 2007;Lercher & Pál 2008), recognizing transcription, translation, folding and assembly signals (Lercher & Pál 2008), and otherwise accommodating kinetically and thermodynamically. Most global regulators have evolved vertically, whereas many local regulatory nodes have been acquired by LGT, often simultaneously with the gene(s) they regulate (Price et al 2008).…”