Prophage LambdaSo uses replication interference to suppress reproduction of coexisting temperate phage MuSo2 in Shewanella oneidensis MR‐1

Many bacterial genomes carry multiple prophages that compete with each other, potentially affecting the physiology, fitness, and pathogenicity of their hosts. However, molecular mechanisms of such prophage–prophage conflicts remain poorly understood. The genome of Shewanella oneidensis MR‐1, a Gammaproteobacterium residing in aquatic environments and notable for its ability to reduce metal ions, harbours four prophages, two of which (LambdaSo and MuSo2) form infectious virions during biofilm formation. Here, we constructed indicator strains of LambdaSo and MuSo2 by deleting the corresponding prophages from the MR‐1 chromosome and investigated their reproduction. Interestingly, the fitness of MuSo2 increased in the absence of LambdaSo, suggesting that prophage LambdaSo repressed MuSo2 reproduction. Partial deletion of LambdaSo from the MR‐1 chromosome revealed that gene cluster R of LambdaSo, which was responsible for the switch to the lytic cycle and LambdaSo genome replication initiation, was necessary and sufficient to repress MuSo2. Furthermore, activation of cluster R genes facilitated replication of cluster R‐encoding DNA and inhibited host and MuSo2 DNA replication. These findings suggest that LambdaSo represses MuSo2 propagation by inhibiting DNA replication during simultaneous induction. We predict that such a mechanism of inter‐prophage interference is more widespread in bacteria than currently appreciated.