Multi-conflict islands are a widespread trend within Serratia spp

Bacteria carry numerous anti-phage systems in “defense islands” or hotspots. Recent studies have delineated the content and boundaries of these islands in various species, revealing instances of islands that encode additional factors, including antibiotic resistance genes, stress genes, type VI secretion system (T6SS)-dependent effectors, and virulence factors. Our study identifies three defense islands in the Serratia genus with a mixed cargo of anti-phage systems, virulence factors, and different types of anti-bacterial modules, revealing a widespread trend of co-accumulation that extends beyond T6SS-dependent effectors to colicins and contact-dependent inhibition systems. We further report the identification of four distinct anti-phage system/subtypes, including a previously unreported Toll/interleukin (IL)-1 receptor (TIR)-domain-containing system with population-wide immunity, and two loci co-opting a predicted T6SS-related protein for phage defense. This study enhances our understanding of the protein domains that can be co-opted for phage defense, resulting in a highly diversified anti-phage arsenal. [Display omitted] •Three Serratia islands colocalize anti-phage systems with anti-bacterial and virulence factors•This study shows genus-focused studies help uncover previously undiscovered anti-phage systems•SDIC1 combines TIR and ubiquitin ligase, uncovering toxin inhibition through ubiquitination•SDIC4 employs a VasI-like domain to reduce phage adsorption across two distinct subtypes Cummins, Songra et al. identify three Serratia defense islands co-localizing anti-phage systems, virulence factors, and anti-bacterial factors. These islands provide a resource for discovering previously unreported systems, including four newly identified anti-phage systems (SDIC1–4). Notably, SDIC1 and SDIC4 exhibit distinct mechanisms, with SDIC1 using ubiquitination to inhibit its toxin in a TA-like manner.