Hijacking the Hijackers: Escherichia coli Pathogenicity Islands Redirect Helper Phage Packaging for Their Own Benefit

• Published in: Molecular cell Vol. 75; no. 5; pp. 1020 - 1030.e4
• Main Authors: Fillol-Salom, Alfred, Bacarizo, Julio, Alqasmi, Mohammed, Ciges-Tomas, J. Rafael, Martínez-Rubio, Roser, Roszak, Aleksander W., Cogdell, Richard J., Chen, John, Marina, Alberto, Penadés, José R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.09.2019; Cell Press
• Subjects: bacteriophage; Bacteriophages - physiology; DNA, Viral - genetics; DNA, Viral - metabolism; Endodeoxyribonucleases - genetics; Endodeoxyribonucleases - metabolism; Escherichia coli - genetics; Escherichia coli - virology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; evolution; gene transfer; Genomic Islands; pathogenicity islands; PICI; pirating; TerS; transduction; Viral Proteins - genetics; Viral Proteins - metabolism; virulence; Virus Assembly - physiology; pirating; virulence; gene transfer; pathogenicity islands; TerS; transduction; PICI; evolution; bacteriophage
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2019.06.017

Phage-inducible chromosomal islands (PICIs) represent a novel and universal class of mobile genetic elements, which have broad impact on bacterial virulence. In spite of their relevance, how the Gram-negative PICIs hijack the phage machinery for their own specific packaging and how they block phage reproduction remains to be determined. Using genetic and structural analyses, we solve the mystery here by showing that the Gram-negative PICIs encode a protein that simultaneously performs these processes. This protein, which we have named Rpp (for redirecting phage packaging), interacts with the phage terminase small subunit, forming a heterocomplex. This complex is unable to recognize the phage DNA, blocking phage packaging, but specifically binds to the PICI genome, promoting PICI packaging. Our studies reveal the mechanism of action that allows PICI dissemination in nature, introducing a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial pathogen evolution. [Display omitted] •PICI Rpp protein promotes PICI transfer while blocking phage reproduction•Rpp forms a heterocomplex with helper phage TerS•Crystal structures of Rpp alone or complexed with TerS were determined•TerS complexed with Rpp switches specificity from the phage DNA to the PICI genome Fillol-Salom et al. report that Gram-negative PICIs employ the Rpp protein to block helper phage reproduction. Rpp binds to helper phage TerS, and the Rpp-TerS heterocomplex enables PICIs to hijack the phage machinery for their own packaging. These findings reveal a mechanism used by Gram-negative PICIs to spread in nature.