Remote extracellular attacks on bacteriophage

Bacteriophages and their hosts co-evolve while exploiting and defending against the other, respectively. Known anti-phage defences prevent attachment to the cell or target phage nucleic acids within the cell; variation in such defences shapes phage host range. While investigating the host range of the virulent myxophage Mx1 among natural isolates of the social bacterium Myxococcus xanthus, we found not only that Mx1’s host range is very limited, but also that Mx1 is itself antagonised by most isolates. These antagonisms inactivate many phages and appear mediated by both cell-bound compounds and diffusive polypeptides. In harming phage before infection, anti-phage public goods represent a new category of defence. While some isolates secrete anti-phage compounds only constitutively, others do so facultatively in response to Mx1, behaviour suggestive of anti-phage adaptation. M. xanthus also alters the heat-stress-tolerance of phage surviving initial interaction. Such effects vary greatly across genotypes; some genotypes failing to antagonise Mx1 in direct encounters nonetheless reduce phage tolerance of later heat stress. Collectively, our results suggest that M. xanthus may have adapted to produce extracellular anti-phage agents that inactivate some phages and weaken others. Secreted anti-phage agents raise intriguing questions regarding the costs and benefits of extracellular versus cell-associated anti-phage defences.