Temporal GWAS identifies a widely distributed novel protein Stv contributing to pathogen success in Shigella spp.

Abstract

Shigella has emerged as a successful pathogen posing a threat to human health worldwide in the recent years. The rise of Shigella over the years has variably been attributed to AMR genes, virulence, and bacterial competition factor but no method has taken a function-agnostic approach to look for factors associated with modern variants of the pathogens. To address this gap, here we combined historical and modern isolate collections to identify such factors through a novel approach, termed temporal GWAS (tGWAS). Our analyses identified a novel putative adhesin gene, which we called stv that was associated with time of isolation and concentrated in expanding lineages of Shigella spp, as well as widely distributed in other bacterial species. We confirmed that stv is carried on a small 2689bp plasmid and in silico analyses revealed that Stv contained a new protein domain that was in combination with other domains in a manner suggestive of a secreted bacterial toxin. However, an all-proteome AlphaFold interaction screen indicated a high likelihood of interactions with fimbrial proteins, despite fimbrae thought to be defunct in Shigella sp. Collectively, these findings suggest that Stv is a novel protein domain with a likely role in Shigella success that is also widely distributed in other species.