Poly-immunity arrays associated with Rhs toxins confer wide protection against competitors

Bacterial genomes evolve under intense competition with diverse microorganisms. Polymorphic toxins are one of the best examples for demonstrating the intensity of this process. They comprise hypervariable C-terminal domains, encoding a broad range of toxic activities. These toxins are typically accompanied by highly specific immunity proteins encoded immediately downstream, which protect the producing bacteria from self-intoxication or fratricide. Here, we show that Photorhabdus and Xenorhabdus spp. genomes harbor extensive arrays of clustered immunity genes encoding proteins that neutralize type VI secretion system (T6SS) rearrangement hot spot (Rhs) polymorphic toxins secreted by closely related species. These immunity genes derive from ancient toxin-immunity pairs, yet only the immunity components are conserved, highlighting their protective role. Consistent with this, many of these immunity genes are expressed under steady-state conditions. Finally, we identify novel genetic elements conserved in several bacterial genera, termed Xer passenger cassettes (XPCs), which associate with both Rhs and the contact-dependent growth inhibition (CDI) polymorphic toxins, suggesting a potential role in their diversification and horizontal dissemination.