Anti-Phage Defence

the maxwell lab

Phages, which outnumber bacteria ten-fold in most environments, are one of the most serious threats to bacterial survival. As a result, bacteria have evolved a wide range of systems to defend themselves from phage infection.

All previously characterized anti-phage defense mechanisms, such as restriction enzymes and CRISPR-Cas systems, require protein components to function. We recently discovered that Streptomyces, a group of bacteria that live in the soil, also use chemicals known as secondary metabolites to defend themselves from phage attack. These secondary metabolites are produced by cells and secreted into the environment where they can be taken up by surrounding cells. This serves to protect the bacterial colony as a whole, even if only some cells are producing the secondary metabolites at any given time.

Nature Podcast

Our work identified a group of molecules, known as anthracyclines, that have the ability to protect Streptomyces from phages. These molecules, which are widely used in cancer treatment, interact with the infecting phage genome and prevent it from replicating. This preferenital activity against rapidly replicating phage genomes may help explain the longstanding question of why bacteria are such a great source of anti-cancer drugs.

Ongoing work in the lab aims to address some of the many questions that remain outstanding. How diverse are the anti-phage secondary metabolites that Streptomyces produce? Are there other unrelated groups of molecules? How widespread is this mechanism among bacteria? Have phages evolved counter-defenses to help protect them from this chemical attack?

We're looking for talented scientists to help us answer these and many more questions about this phage-host evolutionary arms race.