Harmful blooms caused by diazotrophic (nitrogen-fixing) Cyanobacteria are becoming increasingly frequent and negatively impact aquatic environments worldwide. Cyanophages (viruses infecting Cyanobacteria) can potentially regulate cyanobacterial blooms, yet Cyanobacteria can rapidly acquire mutations that provide protection against phage infection. Here, we provide novel insights into cyanophage:Cyanobacteria interactions by characterizing the resistance to phages in two species of diazotrophic Cyanobacteria: Nostoc sp. and Cylindrospermopsis raciborskii. Our results demonstrate that phage resistance is associated with a fitness tradeoff by which resistant Cyanobacteria have reduced ability to fix nitrogen and/or to survive nitrogen starvation. Furthermore, we use whole-genome sequence analysis of 58 Nostoc-resistant strains to identify several mutations associated with phage resistance, including in cell surface-related genes and regulatory genes involved in the development and function of heterocysts (cells specialized in nitrogen fixation). Finally, we employ phylogenetic analyses to show that most of these resistance genes are accessory genes whose evolution is impacted by lateral gene transfer events. Together, these results further our understanding of the interplay between diazotrophic Cyanobacteria and their phages and suggest that a tradeoff between phage resistance and nitrogen fixation affects the evolution of cell surface-related genes and of genes involved in heterocyst differentiation and nitrogen fixation.
Keywords: Cyanobacteria; cost of resistance; genome evolution; nitrogen fixation; phage; resistance; tradeoff.
© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.