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

Alfred Fillol-Salom,John Chen,Mohammed Alqasmi,Alberto Marina,J Rafael Ciges-Tomas,Roser Martínez-Rubio,José R Penadés,Julio Bacarizo,Aleksander W Roszak,Richard J Cogdell

doi:10.1016/j.molcel.2019.06.017

Abstract

SummaryPhage-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.

Highlights

The acquisition of mobile genetic elements (MGEs) that carry virulence factors is a major event that can transform an avirulent or weakly virulent strain into a multi-resistant hypervirulent strain
The biology of the Gram-positive phageinducible chromosomal islands (PICIs) has been extensively studied (Penades and Christie, 2015), it remains a mystery how the PICI elements present in the Gram-negative bacteria hijack the phage machinery for their preferential packaging and transfer in nature and how these elements interfere with helper phage reproduction
Most Gram-positive PICIs interfere with phage reproduction by promoting the formation of small PICI capsids that are much too small for the larger phage genomes (Carpena et al, 2016; Martınez-Rubio et al, 2017; Matos et al, 2013; Quiles-Puchalt et al, 2014; Ruzin et al, 2001; Ubeda et al, 2005), that was not the case for the EcCICFT073 element, which is packaged into phage-sized capsid (Fillol-Salom et al, 2018)

Summary

Introduction

The acquisition of mobile genetic elements (MGEs) that carry virulence factors is a major event that can transform an avirulent or weakly virulent strain into a multi-resistant hypervirulent strain. The biology of the Gram-positive PICIs has been extensively studied (Penades and Christie, 2015), it remains a mystery how the PICI elements present in the Gram-negative bacteria hijack the phage machinery for their preferential packaging and transfer in nature and how these elements interfere with helper phage reproduction. To address these questions, we have analyzed one of these elements, EcCICFT073, present in the uropathogenic Escherichia coli CFT073 strain. Most Gram-positive PICIs interfere with phage reproduction by promoting the formation of small PICI capsids that are much too small for the larger phage genomes (Carpena et al, 2016; Martınez-Rubio et al, 2017; Matos et al, 2013; Quiles-Puchalt et al, 2014; Ruzin et al, 2001; Ubeda et al, 2005), that was not the case for the EcCICFT073 element, which is packaged into phage-sized capsid (Fillol-Salom et al, 2018)

Methods

Results

Conclusion