Investigations into the Phage-Host Dynamics of Streptomyces

Bacteriophage (phage) infection poses a major risk to bacteria, and as such most bacteria have evolved myriad defences to protect against it. Streptomyces bacteria are a genus of the order Actinomycetales and are characterized by their complex lifecycle and prodigious production of secondary or specialized metabolites, chemicals that help them compete against other microbes sharing their environment. Here, I show that Streptomyces utilize secondary metabolites to protect their communities against phage infection. In particular, DNA intercalating agents like daunorubicin, actinomycin, and cosmomycin are secreted into the environment by mature bacterial cells and inhibit phage replication to provide a chemically based community defence. Since Streptomyces utilize secondary metabolites to defend against phage infection, I examined phenotypic changes in several Streptomyces species to determine whether phage infection altered their secondary metabolism. I determined that several Streptomyces species produce colored metabolites in response to phage infection, and I sequenced the genomes of 12 new Streptomyces phages to investigate the phages themselves and gain insight into any hypothetical phage genes that may play a role in alteration of host metabolism. One gene of particular interest is Lsr2, a bacterial gene that is present in 11 of our sequenced phages. Lsr2 is a xenogeneic silencing protein that silences foreign DNA in bacteria. Xenogeneic silencers have been shown to bind to and silence prophage genes genomes and many phages encode for proteins that inhibit xenogeneic silencers, indicating that xenogeneic silencers may have a role in anti-phage defence. However, deletion of these genes in vivo has been shown to result in a decrease in the efficiency of phage infection and Lsr2 was recently shown to be necessary for infection of Mycobacterium smegmatis by several phages. I show that the Lsr2 and Lsr2-like (LsrL) proteins encoded by Streptomyces venezuelae play an active role in anti-phage defence, and that phage-encoded homologs of Lsr2 provide a counter for this defence. Overall, this work has explored the phage-host dynamics between Streptomyces bacteria and the phages that infect them, and broadened our knowledge of Streptomyces, Streptomcyes phages, and anti-phage defence.

Department dc:contributor.department

Biochemistry

Year dc:date.issued

2023

Author dc:creator

• Kronheim, Sarah

Advisor dc:contributor.advisor

• Maxwell, Karen L

• Bacteriophage
• Streptomyces

Handle dc:identifier.uri

http://hdl.handle.net/1807/140452

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/140452