Genome‐Wide In Silico Analysis of the Type VI Secretion System (T6SS) Within the <i>Morganella</i> Genus

Morganella spp., part of the Morganellaceae family, are opportunistic pathogens commonly found in the human gut microbiota. They are highly adaptable, cause various types of infections, and are difficult to treat due to virulence factors and resistance genes. In 2017, Morganella became part of the WHO Bacterial Pathogen Priority List (BPPL). In 2024, a genomic study revealed significant differences between clinically relevant species, particularly between M. sibonii and M. morganii, with M. sibonii possessing a unique type VI secretion system (T6SS) operon. This study aimed to explore the distribution and diversity of T6SS in Morganella species. A retrospective analysis of 293 Morganella genomes from 1966 to 2023 was conducted. The T6SS clusters and subtypes were annotated using the SecReT6 platform and RAST, with phylogenetic analysis performed on tssB genes. Putative effectors and immunity proteins were identified through in silico analysis using BlastP and Alphafold. We identified that M. sibonii isolates possess four T6SS clusters of subtypes i1, i3 v.1, i3 v.2, and i5. In contrast, most M. morganii isolates lacked T6SS, with only one-third containing a subtype i1 T6SS. Notably, M. morganii frequently (95%, 117/123 effectors) harbored a T6SS-predicted TseV effector, while M. sibonii exhibited a greater diversity of effectors. This study highlights species-specific T6SS patterns among Morganella genus and suggests that T6SS might play a crucial role in bacterial lifestyle competition and host-pathogen interactions. It paves the way for future research on Morganella pathogenicity.