Remote extracellular attacks on bacteriophage

Bacteriophages and their hosts co-evolve while exploiting and defending against the other, respectively. Anti-phage defences generally prevent attachment to cells or post-injection replication; variation in such defences shapes phage host range. While investigating the host range of the virulent myxophage Mx1 among natural-isolate strains of the social bacterium Myxococcus xanthus, we found that most strains render large majorities (>99%) of free phage particles non-viable – unable to infect a permissive host. Culture supernatants from all inactivating strains neutralized free phage, implicating diffusible anti-phage compounds, alth...  more

Bacteriophages and their hosts co-evolve while exploiting and defending against the other, respectively. Anti-phage defences generally prevent attachment to cells or post-injection replication; variation in such defences shapes phage host range. While investigating the host range of the virulent myxophage Mx1 among natural-isolate strains of the social bacterium Myxococcus xanthus, we found that most strains render large majorities (>99%) of free phage particles non-viable – unable to infect a permissive host. Culture supernatants from all inactivating strains neutralized free phage, implicating diffusible anti-phage compounds, although some strains appear to also employ cell-bound anti-phage compounds. Some M. xanthus strains appear to produce phage-inactivating compounds only constitutively while others facultatively increase their ability to neutralize phage upon encountering Mx1. Importantly, we show that many M. xanthus strains physically harm free phage; phages among the small minorities surviving an encounter with a phage-inactivating strain were often rendered unable to survive heat stress. The nature and magnitude of anti-phage activity vary markedly across M. xanthus genotypes, including differences in diffusible vs. contact-dependent inactivation, constitutive vs. inducible production, and damage-induced reduction of phage heat-tolerance. Our results demonstrate new forms of anti-phage defence by bacteria, including physical damage of free phage associated with inactivation of the vast majority of extracellular phage particles in the local environment prior to adsorption. They also suggest that some M. xanthus strains may be evolutionarily adapted to exert these effects and raise intriguing questions regarding the costs and benefits of extracellular versus cell-associated anti-phage defences.