The discovery of a <i>Legionella</i> phage explains a key determinant of human disease

Host cells provide intracellular bacteria with protection from harsh environmental conditions and immune responses, but for many intracellular pathogens, this protection does not appear to be absolute as once thought. Bacteriophages that can kill bacteria inside host cells have been identified for pathogens including <i>Salmonella</i>, <i>Mycobacterium</i>, and <i>Chlamydia</i> species. Even in pathogens for which no stable phages have been isolated, such as <i>Legionella pneumophila</i>, the presence of phage defense systems suggests phage susceptibility. Here, we report the stable isolation of <i>Legionella</i> bacteriophage LME-1 (<i>Legionella</i> mobile element-1) and its impact on bacterial virulence in humans. Cryo-electron microscopy of the capsid (2.1 angstroms) and portal-tail complex (1.9 angstroms) reveals an unambiguous phage particle with T7-like morphology. Characterizing the host range of this phage, we make a serendipitous finding that links the acquisition of a phage defense mechanism to the formation of a virulent clade of <i>L. pneumophila</i> responsible for 80% of all Legionnaires' disease.