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Blower, T. R.

Publications and source records attributed to Blower, T. R..

3 recordsLinked to original sources

Temporal GWAS identifies a widely distributed putative adhesin contributing to pathogen success in Shigella spp.

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.

genomics↗

A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands

AO_SCPLOWBSTRACTC_SCPLOWBacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into "defence islands", providing a potentially synergistic level of protection against a wider range of assailants. However, there is a comparative paucity of information on how expression of these defence systems is controlled. Here, we functionally characterise a transcriptional regulator, BrxR, encoded within a recently described phage defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a combination of reporters and electrophoretic mobility shift assays, we discovered that BrxR acts as a repressor. We present the structure of BrxR to 2.15 [A], the first structure of this family of transcription factors, and pinpoint a likely binding site for ligands within the WYL-domain. Bioinformatic analyses demonstrated that BrxR homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localised with a diverse array of known phage defence systems, either alone or clustered into defence islands. BrxR is a novel regulator that reveals a common mechanism for controlling the expression of the bacterial phage defence arsenal.

microbiology↗

Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing bloodstream infection in Malawi

In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting S. Typhimurium and S. Enteritidis, from water sources in Malawi and the UK. The phages were classified in three major phylogenetic clusters that were geographically distributed. In terms of host range, Cluster 1 phages were able to infect all bacterial hosts tested, whereas Clusters 2 and 3 had a more restricted profile. Cluster 3 contained two sub-clusters, and 3.b contained the most novel isolates. This study represents the first exploration of the potential for phages to target the lineages of Salmonella that are responsible for bloodstream infections in sub-Saharan Africa.

microbiology↗