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Biology subjects

De Silva, P. M.

Publications and source records attributed to De Silva, P. M..

2 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 tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella

Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two Shigella plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation, and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation rates for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.

microbiology↗