Dormant bacteria eliminate RNA phages through cumulative ROS-mediated RNA damage

Phages are the most abundant biological entities on Earth; yet, RNA phages are rarely isolated and are scarce compared to their DNA counterparts-a long-standing mystery in phage biology. Here, we demonstrate that while RNA phages efficiently infect growing bacteria, they are gradually eliminated inside dormant bacteria through weak and time-dependent reactive oxygen species (ROS) mediated damage. The RNA phages decline over days rather than through immediate clearance inside dormant bacteria. Accordingly, scavenging ROS with mannitol or overexpressing ROS degradation enzymes AhpB/TrxB2 rescues RNA phages from elimination. Crucially, because the underlying ROS-mediated RNA damage is minimal, co-infection by multiple virions of an RNA phage allows a fraction of RNA phages to survive inside dormant bacteria. Given that most environmental bacteria are dormant and subject to heterogeneous phage infection, this copy number-dependent vulnerability offers a possible explanation for the scarcity, but not elimination, of RNA phages in nature.