Impact of Xenogeneic Silencing on Phage–Host Interactions

Abstract

Phages, viruses that prey on bacteria, are the most abundant and diverse inhabitants of the Earth. Temperate bacteriophages can integrate into the host genome and, as so-called prophages, maintain a long-term association with their host. The close relationship between host and virus has significantly shaped microbial evolution and phage elements may benefit their host by providing new functions. Nevertheless, the strong activity of phage promoters and potentially toxic gene products may impose a severe fitness burden and must be tightly controlled. In this context, xenogeneic silencing (XS) proteins, which can recognize foreign DNA elements, play an important role in the acquisition of novel genetic information and facilitate the evolution of regulatory networks. Currently known XS proteins fall into four classes (H-NS, MvaT, Rok and Lsr2) and have been shown to follow a similar mode of action by binding to AT-rich DNA and forming an oligomeric nucleoprotein complex that silences gene expression. In this review, we focus on the role of XS proteins in phage-host interactions by highlighting the important function of XS proteins in maintaining the lysogenic state and by providing examples of how phages fight back by encoding inhibitory proteins that disrupt XS functions in the host. Sequence analysis of available phage genomes revealed the presence of genes encoding Lsr2-type proteins in the genomes of phages infecting Actinobacteria. These data provide an interesting perspective for future studies to elucidate the impact of phage-encoded XS homologs on the phage life cycle and phage-host interactions. "You have a grand gift for silence, Watson. It makes you quite invaluable as a companion."

Horizontally Acquired Homologs of Xenogeneic Silencers: Modulators of Gene Expression Encoded by Plasmids, Phages and Genomic Islands

“…Remarkably, the GC content of the EARL islands is significantly lower than the median value of the other Enterobacteriaceae GIs (Figure 2A), remaining low even when the host chromosomal GC increases ( Figure 2B). This feature agrees with what has been reported for plasmids and actinobacteriophages that encode homologs of H-NS and Lsr2, respectively, which have a lower GC content compared with those which do not encode an XS homolog [63]. The low GC of the EARL islands and its narrow range of variability (35.7-39.2%) could be the result of their relatively rapid spread within Enterobacteriaceae, an idea supported by the fact that ROD21 can be transferred by conjugation [106] and that the ICEKp258.2 island from K. pneumoniae ST258, which may represent an early member of the SpnT/type-3 R-M-encoding clade within the EARL phylogeny [50], was acquired by this sequence type approximately 20-25 years ago [120][121][122].…”

“…The effect of the truncated version of CGP3 underlines the importance of dimerization/oligomerization in the activity of xenogeneic silencers and their horizontally acquired homologs. A recent review article reported that horizontally acquired Lsr2 homologs are encoded by a great number of other actinobacteriophages sequenced to date, whose hosts belong to genera Mycobacterium, Microbacterium, Gordonia, and Streptomyces [63]. As described by the authors of that review, the finding that CgpS is essential to C. glutamicum only when CGP3 is present [72], together with the relatively high frequency of Lsr2 homologs (Lsr2 Actinophage ) in lysogenic versus lytic phages, suggests that these XS homologs play a major role in the integration of prophages in bacteria [63].…”

From Sequence to Information

“…in amino acid compositions. Like the LSR2 protein, which is a transcription silencer found in Actiobacteria, in which it binds AT reach DNA and silence its transcription [98,97,39]. This example illustrates how information stored in the sequence can drastically differ between the different levels of observations.…”

Deciphering the rules underlying xenogeneic silencing and counter-silencing of Lsr2-like proteins

“…The essentiality of Lsr2 for this human pathogen makes this XS protein a highly promising drug candidate (37). In Corynebacterium glutamicum the Lsr2-like XS protein CgpS was also shown to play an essential role as a silencer of cryptic prophage elements, whose entrance into the lytic cycle would otherwise cause cell death (4, 38). In contrast to mycobacteria and corynebacterial species, Streptomyces typically encode two Lsr2-like proteins.…”