Viral DNA and prophage-like elements can make up 20% of the entire bacterial genome and may significantly contribute to their host’s fitness (Nanda et al., 2015). However, the acquisition of new genetic elements also bears risks for their hosts since their activation gene expression may cause high metabolic costs or even lead to cell death and lysis. To enable the controlled integration of newly acquired DNA into the host’s regulatory network, cells have evolved small nucleoid-associated xenogeneic silencers. These proteins possess the characteristic to target and suppress foreign AT-rich DNA, thereby contributing to the mutual adaptation (Navarre et al., 2007).
In our studies, we use the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 as model system to investigate prophage-host regulatory interaction. The genome of ATCC 13032 contains three cryptic prophages (CGP1-3), of which CGP3, the largest of those (῀190 kb) was shown to undergo spontaneous activation in a small fraction of cells (Helfrich et al., 2015, Frunzke et ., 2008). However, the molecular factors controlling CGP3 activity are currently not known.
Recently, we identified a small nucleoid-associated protein, named CgpS, which is encoded on the CGP3 prophage island and shares intriguing similarities with the mycobacterial xenogeneic silencer Lsr2. In our studies, we could show that CgpS is an essential gene due to its function as a silencer of cryptic phage elements in C. glutamicum. Genome-wide binding analyses displayed the preferred association to AT-rich elements, especially to CGP3, but also to other regions of foreign origin. Bioinformatical analysis revealed orthologous proteins in almost all Actinomycetes, but remarkably, also in several phage and prophage genomes. Our results emphasize CgpS as a key factor for the control of CGP3 activity and highlight the importance of small nucleoid-associated proteins for the control of foreign DNA in bacterial host strains.